Strain Name:

B6.129-Arntltm1Bra/J

Stock Number:

009100

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The Arntl knock-out strain may be useful in studies of circadian rhythm, arthritis, ankylosis, and glucose homeostasis.

Description

Strain Information

Type Congenic; Targeted Mutation;
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Mating System+/+ sibling x Heterozygote         (Female x Male)   09-JUN-09
Specieslaboratory mouse
GenerationN15+F6 (08-JUN-09)
Generation Definitions
 
Donating InvestigatorDr. Joseph S. Takahashi,   Univ Texas Southwestern Medical Ctr

Description
These targeted mutation mice exhibit a loss of both behavioral and molecular circadian rhythms. When placed in constant darkness, the mice undergo an immediate loss of circadian rhythmicity. Locomotor activity is impaired in both light and constant dark cycles.

Reduced total activity is seen as the mice age. They display a progressive noninflammatory arthropathy. Little pathology is seen prior to 11 weeks of age, but virtually all homozygotes develop joint ankylosis due to flowing ossification of ligaments and tendons by 35 weeks of age. Bone density and articular cartilage are unaffected.

Inactivation of the gene suppresses diurnal variation in glucose and triglycerides. Gluconeogenesis is abolished in homozygotes, but the counterregulatory response of corticosterone and glucagon to insulin-induced hypoglycemia is retained. Homozygotes are viable but not fertile and have an increased mortality rate after 26 weeks of age. A truncated, non-functional protein is produced. This strain may be useful in studies of circadian rhythm, arthritis, ankylosis, and glucose homeostasis.

Development
The helix-loop-helix domain within exon 4 and all of exon 5 were replaced with a neomycin resistance gene cassette. 129/Sv-derived GS1 embryonic stem (ES) cells were used to create the mutation. This line was backcrossed 14 times to C57BL/6 by the donating laboratory.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Arntl
007668   B6.129S4(Cg)-Arntltm1Weit/J
007618   B6.Cg-Tg(tetO-Arntl)1Jt/J
View Strains carrying other alleles of Arntl     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.
Priapism, Familial Idiopathic
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Arntltm1Bra/Arntltm1Bra

        B6.129-Arntltm1Bra
  • mortality/aging
  • premature aging
    • display age related sarcopenia and osteoporosis at 40 weeks of age   (MGI Ref ID J:110697)
    • mice display a number of age related phenotypes at an earlier age compared to wild-type controls   (MGI Ref ID J:110697)
    • mice exhibit age-induced circulatory changes showing accelerated thrombogenicity at an earlier age than wild-type mice   (MGI Ref ID J:191844)
  • premature death
    • 29% of animals do not survive for 10 months   (MGI Ref ID J:116189)
    • require euthanasia between 26 - 45 weeks of age due to dehydration and failure to thrive   (MGI Ref ID J:97108)
    • most die between 26 and 52 weeks of age   (MGI Ref ID J:110697)
    • average lifespan is 37 +/- 12 weeks   (MGI Ref ID J:110697)
    • maximum lifespan is 72 weeks of age   (MGI Ref ID J:110697)
  • behavior/neurological phenotype
  • abnormal circadian rhythm
    • diurnal variation in activity is abolished   (MGI Ref ID J:125921)
    • however, ultradian rhythms are maintained and are stronger than any residual circadian rhythms   (MGI Ref ID J:125921)
    • abnormal circadian regulation of heart rate
      • diurnal variation in heart rate is abolished   (MGI Ref ID J:125921)
    • abnormal circadian regulation of systemic arterial blood pressure
      • diurnal variation in mean arterial pressure is abolished   (MGI Ref ID J:125921)
      • however, ultradian rhythms are maintained and are stronger than any residual circadian rhythms   (MGI Ref ID J:125921)
      • the diurnal variation in restraint induced changes in blood pressure is abolished and the stress induced alteration in blood pressure is lower at ZT12   (MGI Ref ID J:125921)
  • abnormal gait
    • seen in mice over 20 weeks of age   (MGI Ref ID J:97108)
  • abnormal posture
    • seen in mice over 20 weeks of age   (MGI Ref ID J:97108)
  • abnormal tail movements
    • stiff tail after 20 weeks of age   (MGI Ref ID J:97108)
  • impaired righting response
    • seen in mice over 20 weeks of age   (MGI Ref ID J:97108)
    • hindquarters appear more affected than forequarters   (MGI Ref ID J:97108)
  • growth/size/body phenotype
  • decreased body size
    • by 52 weeks of age mice are about half the size of wild-type controls   (MGI Ref ID J:110697)
    • decreased body weight
      • low body weigh relative to wild-type   (MGI Ref ID J:116189)
      • by 26 weeks of age mice weigh 23% less than controls   (MGI Ref ID J:97108)
      • weight loss
        • progressive weight loss starting after 20 weeks of age   (MGI Ref ID J:97108)
        • growth is similar to controls until about 15 weeks of age   (MGI Ref ID J:97108)
        • by 20 weeks of age mice are losing about 0.4g/week   (MGI Ref ID J:97108)
        • starting between 16 to 26 weeks of age   (MGI Ref ID J:110697)
  • decreased total body fat amount
    • at 40 weeks of age   (MGI Ref ID J:110697)
  • postnatal growth retardation
    • starting around 16 - 18 weeks of age   (MGI Ref ID J:110697)
  • skeleton phenotype
  • *normal* skeleton phenotype
    • despite extensive ectopic calcification, bone mineral density is not significantly different from heterozygous controls   (MGI Ref ID J:97108)
    • abnormal joint morphology
      • in the knee by 26 weeks of age increased proliferation is seen in the synovial fibroblasts   (MGI Ref ID J:97108)
      • calcified joint
        • at 6 and 8 weeks of age small areas of calcification extending from the insertion of the calcaneal tendon are seen in the tarsocrural joint   (MGI Ref ID J:97108)
        • by 11 weeks of age, calcified nodules are often seen on the lateral side of the tarsal joint   (MGI Ref ID J:97108)
        • by 26 weeks of age, calcified bridging is seen between tarsal bones   (MGI Ref ID J:97108)
        • progressive calcification is seen in areas around bone cartilage junctions in the rib cage with calcified nodules seen at costal chondral and costal sternal junctions   (MGI Ref ID J:97108)
        • prominent calcified areas extend from the patella as well as along the medial collateral ligament   (MGI Ref ID J:97108)
      • fused joints
        • by 26 weeks of age, calcified bridging is seen between tarsal bones   (MGI Ref ID J:97108)
        • by 35 weeks of age, severe bony ankylosis is seen obscuring the normal anatomy of the tarsocrural joint   (MGI Ref ID J:97108)
        • sacral vertebral fusion
          • large osteophytes bridge the sacral vertebrae and complete fusion is seen between S2 and S3 at 35 weeks of age   (MGI Ref ID J:97108)
        • thoracic vertebral fusion
          • at 35 weeks of age bridging ankylosis is seen on both the dorsal and ventral aspects of the intervertebral joints throughout the thoracic spine   (MGI Ref ID J:97108)
    • abnormal ligament morphology
      • by 26 weeks of age calcification of the medial collateral ligament is seen   (MGI Ref ID J:97108)
      • by 36 weeks of age chondrification and calcification is seen in the lateral collateral ligament and cruciate ligaments   (MGI Ref ID J:97108)
      • calcification/ossification appears to be limited to ligaments closely associated with bone insertion sites in the appendicular and axial skeleton   (MGI Ref ID J:97108)
    • abnormal thoracic cage morphology
      • progressive calcification is seen in areas around bone cartilage junctions in the rib cage with calcified nodules seen at costal chondral and costal sternal junctions   (MGI Ref ID J:97108)
      • costal sternal junctions show proliferative bony bridging from the costal cartilage to the sternum   (MGI Ref ID J:97108)
      • however, muscle fiber attachment appears normal   (MGI Ref ID J:97108)
      • abnormal costal cartilage morphology
        • costal sternal junctions show proliferative bony bridging from the costal cartilage to the sternum   (MGI Ref ID J:97108)
        • costal cartilage shows increased matrix deposition and bone proliferation   (MGI Ref ID J:97108)
      • abnormal rib morphology
        • by 40 weeks of age calcification around bone cartilage junctions results in a severe distortion of the anatomy of the ribs   (MGI Ref ID J:97108)
    • abnormal vertebral column morphology
      • at 35 weeks of age evidence of spinal compression is seen   (MGI Ref ID J:97108)
      • calcified intervertebral disk
        • at 26 weeks of age calcification is seen in the sacral and thoracic regions but not in the lumbar region   (MGI Ref ID J:97108)
    • calcified tendon
      • significant calcaneal tendon calcification   (MGI Ref ID J:116189)
      • by 11 weeks of age calcification of the calcaneal tendon is seen   (MGI Ref ID J:97108)
      • by 26 weeks of age extensive calcification of the calcaneal tendon is seen   (MGI Ref ID J:97108)
      • by 36 weeks of age chondrification and calcification is seen in the lateral collateral ligament and cruciate ligaments   (MGI Ref ID J:97108)
      • calcification/ossification appears to be limited to tendons closely associated with bone insertion sites in the appendicular and axial skeleton   (MGI Ref ID J:97108)
    • ectopic bone formation
      • by 40 weeks of age ectopic ossification is seen in nearly every joint   (MGI Ref ID J:97108)
      • at 26 weeks of age moderate osteophyte formation is seen at the junction of vertebral bodies in the sacral and thoracic regions   (MGI Ref ID J:97108)
      • at 35 weeks of age osteophyte formation is seen at the junction of vertebral bodies in the lumbar region   (MGI Ref ID J:97108)
    • osteoporosis
      • at 40 weeks of age   (MGI Ref ID J:110697)
  • homeostasis/metabolism phenotype
  • abnormal blood coagulation
    • prolongation of the activated partial thrombosplastin time and a shortening of the prothrombin time by 1.6 seconds in 10 week old mice and 0.8 seconds in 30 week old mice, as well as increased plasma fibrinogen, factor VII and VIII levels indicate a hypercoagulable state that increases with age   (MGI Ref ID J:191844)
    • in vascular injury-induced thrombosis, 10 week old mutants show shortened arteriolar and venular occlusion times, indicating early thrombogenicity   (MGI Ref ID J:191844)
    • thrombosis
      • numerous thrombi are seen in the venous sinus of penile sections from older males with priapism; thrombi contain platelets and fibrin and fibrin-rich laminar thrombus formation is seen extensively lining the endothelium   (MGI Ref ID J:191844)
      • in vascular injury-induced thrombosis, 10 week old mutants show shortened arteriolar and venular occlusion times, indicating early thrombogenicity   (MGI Ref ID J:191844)
  • abnormal circulating hormone level
    • levels of osteocalcin are increased   (MGI Ref ID J:97108)
    • abnormal circulating adrenaline level
      • the diurnal variation in restraint induced changes in adrenaline level is abolished   (MGI Ref ID J:125921)
      • decreased circulating adrenaline level
        • at both ZT2 and ZT14   (MGI Ref ID J:125921)
    • decreased circulating noradrenaline level
      • at both Zeitgeber time (ZT) 2 and ZT14   (MGI Ref ID J:125921)
  • abnormal circulating protein level
    • increase in the percentage of plasma factor VII at 30 weeks of age   (MGI Ref ID J:191844)
    • increase in the percentage of plasma factor VIII at 10, but not 30, weeks of age   (MGI Ref ID J:191844)
    • abnormal circulating fibrinogen level
      • increase in the level of plasma fibrinogen at 10 and 30 weeks of age   (MGI Ref ID J:191844)
  • abnormal metabolism
    • at ZT10 in 40 week old mice, the accumulation of reactive oxygen species is increased in the kidney, heart and spleen but decreased in the liver relative to time and age matched controls   (MGI Ref ID J:110697)
    • increase in reactive oxygen species accumulation is age and tissue dependent   (MGI Ref ID J:110697)
  • abnormal nitric oxide homeostasis
    • basal nitric oxide release is attenuated in the thoracic aorta at 30 weeks of age   (MGI Ref ID J:191844)
  • dehydration
    • after 20 weeks of age appear progressively dehydrated   (MGI Ref ID J:97108)
  • reproductive system phenotype
  • decreased testis weight
    • at 40 weeks of age   (MGI Ref ID J:110697)
  • infertility   (MGI Ref ID J:110697)
  • priapism
    • mutants develop spontaneous priapism that increases with age, from 0% at 10 weeks to 8% at 20-25 weeks, and 60% at 25-30 weeks, which is not seen in wild-type mice at any age   (MGI Ref ID J:191844)
    • numerous thrombi are seen in the venous sinus of penile sections; thrombi contain platelets and fibrin and fibrin-rich laminar thrombus formation is seen extensively lining the endothelium   (MGI Ref ID J:191844)
  • small seminal vesicle
    • detectable by 10 weeks of age and becoming more pronounced with age   (MGI Ref ID J:110697)
  • adipose tissue phenotype
  • decreased abdominal adipose tissue amount
    • at 40 weeks of age   (MGI Ref ID J:110697)
  • decreased subcutaneous adipose tissue amount
    • at 40 weeks of age but not at 10 weeks of age   (MGI Ref ID J:110697)
  • decreased total body fat amount
    • at 40 weeks of age   (MGI Ref ID J:110697)
  • hematopoietic system phenotype
  • *normal* hematopoietic system phenotype
    • at 10 and 40 weeks of age no differences are detected in the numbers of red blood cells or platelets   (MGI Ref ID J:110697)
    • abnormal leukocyte tethering or rolling
      • despite an increase in leukocytes, lower numbers of rolling leukocytes over endothelium when activated with A23187 are seen in mutants compared to wild-type at both 10 and 30 weeks of age   (MGI Ref ID J:191844)
    • decreased leukocyte cell number
      • decrease in the number of white blood cells at 40 weeks of age compared to age matched controls   (MGI Ref ID J:110697)
      • decreased basophil cell number
        • decrease in basophils at 30 weeks of age   (MGI Ref ID J:191844)
      • decreased lymphocyte cell number
        • the total number and percentage of lymphocytes are decreased at 40 weeks of age   (MGI Ref ID J:110697)
    • decreased spleen weight
      • at 30 and 40 weeks of age   (MGI Ref ID J:110697)
    • increased leukocyte cell number
      • increase in white blood cell count at 10, but not 30, weeks of age   (MGI Ref ID J:191844)
      • increased eosinophil cell number
        • increase in eosinophils at 10, but not 30, weeks of age   (MGI Ref ID J:191844)
      • increased lymphocyte cell number
        • increase in lymphocytes at 10, but not 30, weeks of age   (MGI Ref ID J:191844)
      • increased monocyte cell number
        • the total number and percentage of monocytes are increased at 40 weeks of age   (MGI Ref ID J:110697)
      • increased neutrophil cell number
        • the total number and percentage of neutrophils are increased at 40 weeks of age   (MGI Ref ID J:110697)
        • neutrophil numbers are increased 2-fold at 10 weeks of age and 1.2-fold at 30 weeks of age   (MGI Ref ID J:191844)
    • increased megakaryocyte cell number
      • density of von Willebrand Factor-positive megakaryocytes in 30 week old bone marrow is higher than in controls   (MGI Ref ID J:191844)
    • increased platelet cell number
      • increase in platelet count at 30 weeks of age   (MGI Ref ID J:191844)
      • despite high platelet numbers at 30 weeks of age, platelet aggregation assays show a normal platelet response to the agonist ADP   (MGI Ref ID J:191844)
  • cardiovascular system phenotype
  • abnormal circadian regulation of heart rate
    • diurnal variation in heart rate is abolished   (MGI Ref ID J:125921)
  • abnormal circadian regulation of systemic arterial blood pressure
    • diurnal variation in mean arterial pressure is abolished   (MGI Ref ID J:125921)
    • however, ultradian rhythms are maintained and are stronger than any residual circadian rhythms   (MGI Ref ID J:125921)
    • the diurnal variation in restraint induced changes in blood pressure is abolished and the stress induced alteration in blood pressure is lower at ZT12   (MGI Ref ID J:125921)
  • abnormal vascular smooth muscle physiology
    • endothelium-dependent vasomotor responses are altered, with an increase of phenylephrine contraction induced by NOS inhibitors and suppression of acetylcholine-muscarinic receptor-induced endothelium-dependent relaxations in aortic rings of mutants, particularly at 30 weeks of age   (MGI Ref ID J:191844)
    • however, mutants exhibit normal contractility of aortic smooth muscle cells as indicated by normal contractile responses to the alpha1-adrenoreceptor agonist phenylephrine when eNOS activity is blocked and normal responsiveness to exogenous nitric oxide released by the nitric oxide donor diethylamine NONOate   (MGI Ref ID J:191844)
    • decreased vasodilation
      • smooth muscle cells exhibit suppression of acetylcholine-muscarinic receptor-induced endothelium-dependent relaxations in aortic rings of mutants, particularly at 30 weeks of age   (MGI Ref ID J:191844)
    • increased vasoconstriction
      • smooth muscle cells show an increase of phenylephrine evoked contraction induced by NOS inhibitors in aortic rings of mutants, particularly at 30 weeks of age   (MGI Ref ID J:191844)
  • corneal vascularization
    • corneal inflammation begins as massive neovascularization   (MGI Ref ID J:110697)
  • decreased heart rate
    • only during the active phase   (MGI Ref ID J:125921)
  • decreased heart weight
    • at 40 weeks of age   (MGI Ref ID J:110697)
  • decreased mean systemic arterial blood pressure
    • expected elevation during the dark phase is absent   (MGI Ref ID J:125921)
    • decreased in both the light and dark phases compared to wild-type controls   (MGI Ref ID J:125921)
  • hypotension   (MGI Ref ID J:125921)
  • vascular smooth muscle cell hyperplasia
    • smooth muscle cell density is higher in aorta segments at 10, but not 30, weeks of age   (MGI Ref ID J:191844)
  • vision/eye phenotype
  • abnormal cornea morphology
    • corneal inflammation begins as ulceration of the outer layer of the cornea   (MGI Ref ID J:110697)
    • keratin deposits are seen   (MGI Ref ID J:110697)
    • abnormal corneal epithelium morphology
    • abnormal corneal stroma morphology
      • ulceration disrupts the stromal structure   (MGI Ref ID J:110697)
    • corneal vascularization
      • corneal inflammation begins as massive neovascularization   (MGI Ref ID J:110697)
    • increased incidence of corneal inflammation
      • at 40 weeks of age over 50% of mice display progressive corneal inflammation   (MGI Ref ID J:110697)
      • corneal inflammation begins as massive neovascularization, lymphoid cell infiltration and ulceration of the outer layer of the cornea   (MGI Ref ID J:110697)
  • abnormal lens morphology
    • the lens posterior zone contains enlarged infiltrating epithelial cells   (MGI Ref ID J:110697)
    • abnormal lens fiber morphology
      • the density of cortical and nucleus fibers is increased   (MGI Ref ID J:110697)
    • cataracts
      • by 30 weeks of age all mice have various grades of cataracts in one or both eyes   (MGI Ref ID J:110697)
  • muscle phenotype
  • abnormal vascular smooth muscle physiology
    • endothelium-dependent vasomotor responses are altered, with an increase of phenylephrine contraction induced by NOS inhibitors and suppression of acetylcholine-muscarinic receptor-induced endothelium-dependent relaxations in aortic rings of mutants, particularly at 30 weeks of age   (MGI Ref ID J:191844)
    • however, mutants exhibit normal contractility of aortic smooth muscle cells as indicated by normal contractile responses to the alpha1-adrenoreceptor agonist phenylephrine when eNOS activity is blocked and normal responsiveness to exogenous nitric oxide released by the nitric oxide donor diethylamine NONOate   (MGI Ref ID J:191844)
    • decreased vasodilation
      • smooth muscle cells exhibit suppression of acetylcholine-muscarinic receptor-induced endothelium-dependent relaxations in aortic rings of mutants, particularly at 30 weeks of age   (MGI Ref ID J:191844)
    • increased vasoconstriction
      • smooth muscle cells show an increase of phenylephrine evoked contraction induced by NOS inhibitors in aortic rings of mutants, particularly at 30 weeks of age   (MGI Ref ID J:191844)
  • calcified tendon
    • significant calcaneal tendon calcification   (MGI Ref ID J:116189)
    • by 11 weeks of age calcification of the calcaneal tendon is seen   (MGI Ref ID J:97108)
    • by 26 weeks of age extensive calcification of the calcaneal tendon is seen   (MGI Ref ID J:97108)
    • by 36 weeks of age chondrification and calcification is seen in the lateral collateral ligament and cruciate ligaments   (MGI Ref ID J:97108)
    • calcification/ossification appears to be limited to tendons closely associated with bone insertion sites in the appendicular and axial skeleton   (MGI Ref ID J:97108)
  • decreased muscle weight
    • at 40 weeks of age   (MGI Ref ID J:110697)
  • vascular smooth muscle cell hyperplasia
    • smooth muscle cell density is higher in aorta segments at 10, but not 30, weeks of age   (MGI Ref ID J:191844)
  • renal/urinary system phenotype
  • decreased kidney weight
    • at 40 weeks of age   (MGI Ref ID J:110697)
  • respiratory system phenotype
  • decreased lung weight
    • at 40 weeks of age   (MGI Ref ID J:110697)
  • immune system phenotype
  • abnormal circulating fibrinogen level
    • increase in the level of plasma fibrinogen at 10 and 30 weeks of age   (MGI Ref ID J:191844)
  • abnormal leukocyte tethering or rolling
    • despite an increase in leukocytes, lower numbers of rolling leukocytes over endothelium when activated with A23187 are seen in mutants compared to wild-type at both 10 and 30 weeks of age   (MGI Ref ID J:191844)
  • decreased leukocyte cell number
    • decrease in the number of white blood cells at 40 weeks of age compared to age matched controls   (MGI Ref ID J:110697)
    • decreased basophil cell number
      • decrease in basophils at 30 weeks of age   (MGI Ref ID J:191844)
    • decreased lymphocyte cell number
      • the total number and percentage of lymphocytes are decreased at 40 weeks of age   (MGI Ref ID J:110697)
  • decreased spleen weight
    • at 30 and 40 weeks of age   (MGI Ref ID J:110697)
  • increased incidence of corneal inflammation
    • at 40 weeks of age over 50% of mice display progressive corneal inflammation   (MGI Ref ID J:110697)
    • corneal inflammation begins as massive neovascularization, lymphoid cell infiltration and ulceration of the outer layer of the cornea   (MGI Ref ID J:110697)
  • increased leukocyte cell number
    • increase in white blood cell count at 10, but not 30, weeks of age   (MGI Ref ID J:191844)
    • increased eosinophil cell number
      • increase in eosinophils at 10, but not 30, weeks of age   (MGI Ref ID J:191844)
    • increased lymphocyte cell number
      • increase in lymphocytes at 10, but not 30, weeks of age   (MGI Ref ID J:191844)
    • increased monocyte cell number
      • the total number and percentage of monocytes are increased at 40 weeks of age   (MGI Ref ID J:110697)
    • increased neutrophil cell number
      • the total number and percentage of neutrophils are increased at 40 weeks of age   (MGI Ref ID J:110697)
      • neutrophil numbers are increased 2-fold at 10 weeks of age and 1.2-fold at 30 weeks of age   (MGI Ref ID J:191844)
  • endocrine/exocrine gland phenotype
  • decreased testis weight
    • at 40 weeks of age   (MGI Ref ID J:110697)
  • small seminal vesicle
    • detectable by 10 weeks of age and becoming more pronounced with age   (MGI Ref ID J:110697)
  • integument phenotype
  • decreased subcutaneous adipose tissue amount
    • at 40 weeks of age but not at 10 weeks of age   (MGI Ref ID J:110697)
  • retarded hair growth
    • at 30 weeks of age hair regrowth after shaving is delayed with only 1 of 5 mice showing partial regrowth after 3 months   (MGI Ref ID J:110697)
    • however, at 10 weeks of age hair regrowth is normal   (MGI Ref ID J:110697)
  • cellular phenotype
  • abnormal leukocyte tethering or rolling
    • despite an increase in leukocytes, lower numbers of rolling leukocytes over endothelium when activated with A23187 are seen in mutants compared to wild-type at both 10 and 30 weeks of age   (MGI Ref ID J:191844)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Arntltm1Bra/Arntl+

        involves: 129 * C57BL/6
  • behavior/neurological phenotype
  • delayed circadian phase
    • significantly enhanced phase delays to light exposure beginning at expected dark (ZT12) with modest enhancements at low irradiance levels and more pronounced delays at higher irradiance levels   (MGI Ref ID J:177916)

Arntltm1Bra/Arntltm1Bra

        involves: 129/Sv
  • reproductive system phenotype
  • decreased uterus weight   (MGI Ref ID J:115188)
  • failure of embryo implantation
    • in the absence of progesterone treatment no implantation sites are seen   (MGI Ref ID J:151819)
    • treatment with progesterone beginning at gestational day 3.5 partially rescues the implantation defect   (MGI Ref ID J:151819)
  • female infertility   (MGI Ref ID J:151819)
  • prolonged estrous cycle
    • cycle length is 49% longer   (MGI Ref ID J:151819)
    • however, the proportion of time spent in each stage is not different from controls   (MGI Ref ID J:151819)
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • no difference is detected in estradiol levels during gestation   (MGI Ref ID J:151819)
    • abnormal circulating protein level
      • at zeitgeber time (ZT) 14, mice exhibit decreased plasminogen activator inhibitor-1 (PAI-1) levels compared with wild-type mice   (MGI Ref ID J:155089)
    • abnormal glucose homeostasis
      • diurnal variation in glucose levels is disrupted   (MGI Ref ID J:131694)
      • abnormal gluconeogenesis
      • increased insulin sensitivity
        • profound hypoglycemic response regardless of the time of day   (MGI Ref ID J:131694)
    • abnormal lipid homeostasis
      • diurnal variation in triglyceride levels is disrupted   (MGI Ref ID J:131694)
    • abnormal response to injury
      • time to thrombotic vascular occlusion (TTVO) subsequent to photochemical injury is shorter than in similarly treated wild-type mice   (MGI Ref ID J:155089)
      • impaired wound healing
        • show severe wound healing defects characterized by lack of epithelial coverage and a highly disorganized granulation tissue   (MGI Ref ID J:193286)
        • most wounds consist mainly of an inflammatory fibrin clot with hardly any fibroblast or keratinocyte proliferation   (MGI Ref ID J:193286)
    • decreased circulating progesterone level
      • levels are lower compared to controls regardless of the time of day on day 3 to day 4 of gestation   (MGI Ref ID J:151819)
  • behavior/neurological phenotype
  • abnormal circadian phase
    • when a 6 hour light pulse is administered 22 days after placement in constant darkness, no effect on locomotor behavior in null mice is observed nor are there phase shifts or suppression of activity, whereas wild-type mice show a ~3.5 hour phase delay after a light pulse   (MGI Ref ID J:66502)
    • few null mutants begin activity within 0.5 hours of lights-off, and 2/17 do not become active at all, whereas all wild-type and heterozygous mice begin activity within 0.5 hours   (MGI Ref ID J:66502)
    • 28% of wheel-running activity of mutants is during the light phase, in contrast to 4.2 or 4.1% during light phase in wild-type or heterozygous mice   (MGI Ref ID J:66502)
  • abnormal locomotor activation
    • level of wheel-running activity in mutants is >3-fold lower during a light cycle and in constant darkness relative to wild-type mice   (MGI Ref ID J:66502)
  • arrhythmic circadian persistence
    • when placed in constant darkness after entrainment to a 12 hour/12 hour light/dark schedule, homozygotes do not express any circadian rhythm or locomotor activity in constant darkness   (MGI Ref ID J:66502)
  • vision/eye phenotype
  • *normal* vision/eye phenotype
    • retinas are indistinguishable in morphology or cellular organization from wild-type littermates   (MGI Ref ID J:124157)
    • abnormal eye electrophysiology
      • under dark-adapted conditions, ERG b-wave is abnormal with 30% reduced amplitude relative to wild-type mice; ratio of b-wave to a-wave amplitude is highly significant   (MGI Ref ID J:124157)
      • under light-adapted conditions, ERG b-wave amplitude is reduced by 60%   (MGI Ref ID J:124157)
  • adipose tissue phenotype
  • increased total fat pad weight   (MGI Ref ID J:115188)
  • skeleton phenotype
  • *normal* skeleton phenotype
    • despite the increase in osteoblast number no increase in bone mass is detected   (MGI Ref ID J:115188)
    • increased bone resorption
      • at 2 months of age   (MGI Ref ID J:115188)
    • increased osteoblast cell number   (MGI Ref ID J:115188)

Arntltm1Bra/Arntltm1Bra

        involves: 129/Sv * C57BL/6
  • mortality/aging
  • premature death
    • survival time of about 6 months   (MGI Ref ID J:135933)
  • behavior/neurological phenotype
  • abnormal circadian rhythm
    • attenuated rhythm of sleep and wakefulness distribution across the 24 h period   (MGI Ref ID J:135933)
  • abnormal sleep pattern
    • display increases in total sleep, sleep fragmentation, and EEG delta power under baseline conditions   (MGI Ref ID J:135933)
    • display attenuated compensatory response following acute sleep deprivation   (MGI Ref ID J:135933)
    • fragmentation of sleep/wake states   (MGI Ref ID J:135933)
  • homeostasis/metabolism phenotype
  • decreased circulating glucose level
    • at 4 months of age   (MGI Ref ID J:135933)
  • decreased plasma anion gap
    • at 4 months of age   (MGI Ref ID J:135933)
  • increased blood urea nitrogen level
    • at 4 months of age   (MGI Ref ID J:135933)
  • increased circulating alanine transaminase level
    • at 4 months of age   (MGI Ref ID J:135933)
  • increased circulating aspartate transaminase level
    • at 4 months of age   (MGI Ref ID J:135933)
  • hematopoietic system phenotype
  • abnormal B cell differentiation
    • partial block in the transition from immature B220low to mature B220high cells   (MGI Ref ID J:118522)
    • transfer of null cells into wild-type mice rescues B cell development and wild-type cells transferred into null mice show a partial block in development suggesting an alteration in the bone marrow microenvironment   (MGI Ref ID J:118522)
  • abnormal T cell subpopulation ratio
    • the percentage of CD4+ T cells is slightly increased in the blood and spleen   (MGI Ref ID J:118522)
    • however, the total number of CD4+ cells is not changed   (MGI Ref ID J:118522)
  • decreased IgG1 level
    • following exposure to human peripheral blood lymphocytes   (MGI Ref ID J:118522)
  • decreased lymphocyte cell number
    • decrease in the number of lymphocytes and white blood cells in the peripheral blood at 4 - 5 months of age   (MGI Ref ID J:135933)
    • decrease in the number of lymphocytes and white blood cells in the peripheral blood   (MGI Ref ID J:118522)
    • decreased B cell number   (MGI Ref ID J:135933)
      • in the peripheral blood and spleen   (MGI Ref ID J:118522)
      • the numbers of B220+ IgM+, CD23+ B220+, and B220+ I-Ab+ cells are decreased in the spleen   (MGI Ref ID J:118522)
      • decreased follicular B cell number   (MGI Ref ID J:118522)
      • decreased transitional stage B cell number
        • decrease in the numbers of type I and type II transitional B cells in the spleen   (MGI Ref ID J:118522)
  • increased neutrophil cell number
    • increase in segmented neutrophil levels at 4 - 5 months of age   (MGI Ref ID J:135933)
  • increased platelet cell number
    • at 4 - 5 months of age   (MGI Ref ID J:135933)
  • immune system phenotype
  • abnormal B cell differentiation
    • partial block in the transition from immature B220low to mature B220high cells   (MGI Ref ID J:118522)
    • transfer of null cells into wild-type mice rescues B cell development and wild-type cells transferred into null mice show a partial block in development suggesting an alteration in the bone marrow microenvironment   (MGI Ref ID J:118522)
  • abnormal T cell subpopulation ratio
    • the percentage of CD4+ T cells is slightly increased in the blood and spleen   (MGI Ref ID J:118522)
    • however, the total number of CD4+ cells is not changed   (MGI Ref ID J:118522)
  • decreased IgG1 level
    • following exposure to human peripheral blood lymphocytes   (MGI Ref ID J:118522)
  • decreased lymphocyte cell number
    • decrease in the number of lymphocytes and white blood cells in the peripheral blood at 4 - 5 months of age   (MGI Ref ID J:135933)
    • decrease in the number of lymphocytes and white blood cells in the peripheral blood   (MGI Ref ID J:118522)
    • decreased B cell number   (MGI Ref ID J:135933)
      • in the peripheral blood and spleen   (MGI Ref ID J:118522)
      • the numbers of B220+ IgM+, CD23+ B220+, and B220+ I-Ab+ cells are decreased in the spleen   (MGI Ref ID J:118522)
      • decreased follicular B cell number   (MGI Ref ID J:118522)
      • decreased transitional stage B cell number
        • decrease in the numbers of type I and type II transitional B cells in the spleen   (MGI Ref ID J:118522)
  • increased neutrophil cell number
    • increase in segmented neutrophil levels at 4 - 5 months of age   (MGI Ref ID J:135933)

Arntltm1Bra/Arntltm1Bra

        involves: 129/Sv * C57BL/6 * C57BL/6J
  • integument phenotype
  • abnormal hair cycle
    • mice exhibit a delay in the first synchronized anagen that persists through out the hair cycle   (MGI Ref ID J:151782)
    • however, the duration of the hair cycle is normal   (MGI Ref ID J:151782)
    • abnormal hair cycle anagen phase
      • the first synchronized anagen is delayed compared to in wild-type mice   (MGI Ref ID J:151782)
  • abnormal hair follicle matrix region morphology
    • hair follicles of mutant mice contain a thickened keratinocyte strand between the dermal papilla and the club hair but lack the highly proliferative matrix required for downward growth of the hair follicle during anagen   (MGI Ref ID J:151782)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Internal/Organ Research
Skeleton
      Bone

Metabolism Research

Neurobiology Research
Circadian Rhythms

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Arntltm1Bra
Allele Name targeted mutation 1, Christopher A Bradfield
Allele Type Targeted (Null/Knockout)
Common Name(s) Bmal1-KO; Mop3-; bmal1-; mMop3-;
Mutation Made ByDr. Christopher Bradfield,   University of Wisconsin Medical School
Strain of Origin129/Sv
ES Cell Line NameGS1
ES Cell Line Strain129/Sv
Gene Symbol and Name Arntl, aryl hydrocarbon receptor nuclear translocator-like
Chromosome 7
Gene Common Name(s) Arnt3; BMAL1; BMAL1c; JAP3; MOP3; PASD3; TIC; bHLHe5;
Molecular Note A portion of exon 4 containing the helix-loop-helix coding domain and all of exon 5 were replaced by a neomycin selection cassette. A larger transcript, resulting from a cryptic splice site between exon 3 and the neomycin resistance gene, was detected byNorthern blot analysis. The polypeptide truncates 15 residues after this splice site, prior to the functional domains encoded by exon 4 in the wild-type locus. [MGI Ref ID J:66502]

Genotyping

Genotyping Information

Genotyping Protocols

Arntltm1Bra, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Bunger MK; Wilsbacher LD; Moran SM; Clendenin C; Radcliffe LA; Hogenesch JB; Simon MC; Takahashi JS; Bradfield CA. 2000. Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103(7):1009-17. [PubMed: 11163178]  [MGI Ref ID J:66502]

Additional References

Bunger MK; Walisser JA; Sullivan R; Manley PA; Moran SM; Kalscheur VL; Colman RJ; Bradfield CA. 2005. Progressive arthropathy in mice with a targeted disruption of the Mop3/Bmal-1 locus. Genesis 41(3):122-32. [PubMed: 15739187]  [MGI Ref ID J:97108]

Rudic RD; McNamara P; Curtis AM; Boston RC; Panda S; Hogenesch JB; Fitzgerald GA. 2004. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol 2(11):e377. [PubMed: 15523558]  [MGI Ref ID J:131694]

Arntltm1Bra related

Andrews JL; Zhang X; McCarthy JJ; McDearmon EL; Hornberger TA; Russell B; Campbell KS; Arbogast S; Reid MB; Walker JR; Hogenesch JB; Takahashi JS; Esser KA. 2010. CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function. Proc Natl Acad Sci U S A 107(44):19090-5. [PubMed: 20956306]  [MGI Ref ID J:166235]

Anea CB; Ali MI; Osmond JM; Sullivan JC; Stepp DW; Merloiu AM; Rudic RD. 2010. Matrix metalloproteinase 2 and 9 dysfunction underlie vascular stiffness in circadian clock mutant mice. Arterioscler Thromb Vasc Biol 30(12):2535-43. [PubMed: 20829506]  [MGI Ref ID J:182097]

Anea CB; Zhang M; Chen F; Ali MI; Hart CM; Stepp DW; Kovalenkov YO; Merloiu AM; Pati P; Fulton D; Rudic RD. 2013. Circadian clock control of Nox4 and reactive oxygen species in the vasculature. PLoS One 8(10):e78626. [PubMed: 24205282]  [MGI Ref ID J:209225]

Anea CB; Zhang M; Stepp DW; Simkins GB; Reed G; Fulton DJ; Rudic RD. 2009. Vascular disease in mice with a dysfunctional circadian clock. Circulation 119(11):1510-7. [PubMed: 19273720]  [MGI Ref ID J:166003]

Boden MJ; Varcoe TJ; Voultsios A; Kennaway DJ. 2010. Reproductive biology of female Bmal1 null mice. Reproduction 139(6):1077-90. [PubMed: 20200203]  [MGI Ref ID J:162882]

Bouchard-Cannon P; Mendoza-Viveros L; Yuen A; Kaern M; Cheng HY. 2013. The circadian molecular clock regulates adult hippocampal neurogenesis by controlling the timing of cell-cycle entry and exit. Cell Rep 5(4):961-73. [PubMed: 24268780]  [MGI Ref ID J:206844]

Bunger MK; Walisser JA; Sullivan R; Manley PA; Moran SM; Kalscheur VL; Colman RJ; Bradfield CA. 2005. Progressive arthropathy in mice with a targeted disruption of the Mop3/Bmal-1 locus. Genesis 41(3):122-32. [PubMed: 15739187]  [MGI Ref ID J:97108]

Cai W; Rambaud J; Teboul M; Masse I; Benoit G; Gustafsson JA; Delaunay F; Laudet V; Pongratz I. 2008. Expression levels of estrogen receptor beta are modulated by components of the molecular clock. Mol Cell Biol 28(2):784-93. [PubMed: 18039858]  [MGI Ref ID J:130393]

Canaple L; Rambaud J; Dkhissi-Benyahya O; Rayet B; Tan NS; Michalik L; Delaunay F; Wahli W; Laudet V. 2006. Reciprocal regulation of brain and muscle Arnt-like protein 1 and peroxisome proliferator-activated receptor alpha defines a novel positive feedback loop in the rodent liver circadian clock. Mol Endocrinol 20(8):1715-27. [PubMed: 16556735]  [MGI Ref ID J:110937]

Cheng B; Anea CB; Yao L; Chen F; Patel V; Merloiu A; Pati P; Caldwell RW; Fulton DJ; Rudic RD. 2011. Tissue-intrinsic dysfunction of circadian clock confers transplant arteriosclerosis. Proc Natl Acad Sci U S A 108(41):17147-52. [PubMed: 21969583]  [MGI Ref ID J:177448]

Chu A; Zhu L; Blum ID; Mai O; Leliavski A; Fahrenkrug J; Oster H; Boehm U; Storch KF. 2013. Global but not gonadotrope-specific disruption of Bmal1 abolishes the luteinizing hormone surge without affecting ovulation. Endocrinology 154(8):2924-35. [PubMed: 23736292]  [MGI Ref ID J:201336]

Curtis AM; Cheng Y; Kapoor S; Reilly D; Price TS; Fitzgerald GA. 2007. Circadian variation of blood pressure and the vascular response to asynchronous stress. Proc Natl Acad Sci U S A 104(9):3450-5. [PubMed: 17360665]  [MGI Ref ID J:125921]

Fu L; Patel MS; Bradley A; Wagner EF; Karsenty G. 2005. The molecular clock mediates leptin-regulated bone formation. Cell 122(5):803-15. [PubMed: 16143109]  [MGI Ref ID J:115188]

Fuller PM; Lu J; Saper CB. 2008. Differential rescue of light- and food-entrainable circadian rhythms. Science 320(5879):1074-7. [PubMed: 18497298]  [MGI Ref ID J:136360]

Fuller PM; Lu J; Saper CB. 2008. Response to Comment on "Differential Rescue of Light- and Food-Entrainable Circadian Rhythms" Science 322:675b.  [MGI Ref ID J:144926]

Geyfman M; Kumar V; Liu Q; Ruiz R; Gordon W; Espitia F; Cam E; Millar SE; Smyth P; Ihler A; Takahashi JS; Andersen B. 2012. Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis. Proc Natl Acad Sci U S A 109(29):11758-63. [PubMed: 22753467]  [MGI Ref ID J:186495]

Grechez-Cassiau A; Rayet B; Guillaumond F; Teboul M; Delaunay F. 2008. The circadian clock component BMAL1 is a critical regulator of p21WAF1/CIP1 expression and hepatocyte proliferation. J Biol Chem 283(8):4535-42. [PubMed: 18086663]  [MGI Ref ID J:141640]

Guillaumond F; Grechez-Cassiau A; Subramaniam M; Brangolo S; Peteri-Brunback B; Staels B; Fievet C; Spelsberg TC; Delaunay F; Teboul M. 2010. Kruppel-like factor KLF10 is a link between the circadian clock and metabolism in liver. Mol Cell Biol 30(12):3059-70. [PubMed: 20385766]  [MGI Ref ID J:162577]

Hemmeryckx B; Hoylaerts MF; Lijnen HR. 2012. Effect of premature aging on murine adipose tissue. Exp Gerontol 47(3):256-62. [PubMed: 22265801]  [MGI Ref ID J:196766]

Hemmeryckx B; Van Hove CE; Fransen P; Emmerechts J; Kauskot A; Bult H; Lijnen HR; Hoylaerts MF. 2011. Progression of the prothrombotic state in aging Bmal1-deficient mice. Arterioscler Thromb Vasc Biol 31(11):2552-9. [PubMed: 21799179]  [MGI Ref ID J:191844]

Husse J; Zhou X; Shostak A; Oster H; Eichele G. 2011. Synaptotagmin10-Cre, a Driver to Disrupt Clock Genes in the SCN. J Biol Rhythms 26(5):379-89. [PubMed: 21921292]  [MGI Ref ID J:175596]

Jeyaraj D; Haldar SM; Wan X; McCauley MD; Ripperger JA; Hu K; Lu Y; Eapen BL; Sharma N; Ficker E; Cutler MJ; Gulick J; Sanbe A; Robbins J; Demolombe S; Kondratov RV; Shea SA; Albrecht U; Wehrens XH; Rosenbaum DS; Jain MK. 2012. Circadian rhythms govern cardiac repolarization and arrhythmogenesis. Nature 483(7387):96-9. [PubMed: 22367544]  [MGI Ref ID J:181622]

Kennaway DJ; Varcoe TJ; Voultsios A; Boden MJ. 2013. Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism. PLoS One 8(6):e65255. [PubMed: 23750248]  [MGI Ref ID J:203142]

Khapre RV; Kondratova AA; Patel S; Dubrovsky Y; Wrobel M; Antoch MP; Kondratov RV. 2014. BMAL1-dependent regulation of the mTOR signaling pathway delays aging. Aging (Albany NY) 6(1):48-57. [PubMed: 24481314]  [MGI Ref ID J:206952]

Khapre RV; Kondratova AA; Susova O; Kondratov RV. 2011. Circadian clock protein BMAL1 regulates cellular senescence in vivo. Cell Cycle 10(23):4162-9. [PubMed: 22101268]  [MGI Ref ID J:207073]

Ko CH; Yamada YR; Welsh DK; Buhr ED; Liu AC; Zhang EE; Ralph MR; Kay SA; Forger DB; Takahashi JS. 2010. Emergence of noise-induced oscillations in the central circadian pacemaker. PLoS Biol 8(10):e1000513. [PubMed: 20967239]  [MGI Ref ID J:167074]

Kondratov RV; Kondratova AA; Gorbacheva VY; Vykhovanets OV; Antoch MP. 2006. Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock. Genes Dev 20(14):1868-73. [PubMed: 16847346]  [MGI Ref ID J:110697]

Kondratov RV; Shamanna RK; Kondratova AA; Gorbacheva VY; Antoch MP. 2006. Dual role of the CLOCK/BMAL1 circadian complex in transcriptional regulation. FASEB J 20(3):530-2. [PubMed: 16507766]  [MGI Ref ID J:129714]

Kowalska E; Ripperger JA; Hoegger DC; Bruegger P; Buch T; Birchler T; Mueller A; Albrecht U; Contaldo C; Brown SA. 2013. Feature Article: NONO couples the circadian clock to the cell cycle. Proc Natl Acad Sci U S A 110(5):1592-9. [PubMed: 23267082]  [MGI Ref ID J:193286]

Lamia KA; Storch KF; Weitz CJ. 2008. Physiological significance of a peripheral tissue circadian clock. Proc Natl Acad Sci U S A 105(39):15172-7. [PubMed: 18779586]  [MGI Ref ID J:141274]

LeSauter J; Lambert CM; Robotham MR; Model Z; Silver R; Weaver DR. 2012. Antibodies for assessing circadian clock proteins in the rodent suprachiasmatic nucleus. PLoS One 7(4):e35938. [PubMed: 22558277]  [MGI Ref ID J:187275]

Lee S; Donehower LA; Herron AJ; Moore DD; Fu L. 2010. Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice. PLoS One 5(6):e10995. [PubMed: 20539819]  [MGI Ref ID J:161808]

Lefta M; Campbell KS; Feng HZ; Jin JP; Esser KA. 2012. Development of dilated cardiomyopathy in Bmal1-deficient mice. Am J Physiol Heart Circ Physiol 303(4):H475-85. [PubMed: 22707558]  [MGI Ref ID J:189081]

Lemos DR; Goodspeed L; Tonelli L; Antoch MP; Ojeda SR; Urbanski HF. 2007. Evidence for circadian regulation of activating transcription factor 5 but not tyrosine hydroxylase by the chromaffin cell clock. Endocrinology 148(12):5811-21. [PubMed: 17823250]  [MGI Ref ID J:131951]

Li JD; Burton KJ; Zhang C; Hu SB; Zhou QY. 2009. Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei. Am J Physiol Regul Integr Comp Physiol 296(3):R824-30. [PubMed: 19052319]  [MGI Ref ID J:148625]

Li S; Yu Q; Wang GX; Lin JD. 2013. The biological clock is regulated by adrenergic signaling in brown fat but is dispensable for cold-induced thermogenesis. PLoS One 8(8):e70109. [PubMed: 23990898]  [MGI Ref ID J:206421]

Lin KK; Kumar V; Geyfman M; Chudova D; Ihler AT; Smyth P; Paus R; Takahashi JS; Andersen B. 2009. Circadian clock genes contribute to the regulation of hair follicle cycling. PLoS Genet 5(7):e1000573. [PubMed: 19629164]  [MGI Ref ID J:151782]

Marcheva B; Ramsey KM; Buhr ED; Kobayashi Y; Su H; Ko CH; Ivanova G; Omura C; Mo S; Vitaterna MH; Lopez JP; Philipson LH; Bradfield CA; Crosby SD; JeBailey L; Wang X; Takahashi JS; Bass J. 2010. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature 466(7306):627-31. [PubMed: 20562852]  [MGI Ref ID J:162641]

McDearmon EL; Patel KN; Ko CH; Walisser JA; Schook AC; Chong JL; Wilsbacher LD; Song EJ; Hong HK; Bradfield CA; Takahashi JS. 2006. Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice. Science 314(5803):1304-8. [PubMed: 17124323]  [MGI Ref ID J:116189]

Mendez-Ferrer S; Lucas D; Battista M; Frenette PS. 2008. Haematopoietic stem cell release is regulated by circadian oscillations. Nature 452(7186):442-7. [PubMed: 18256599]  [MGI Ref ID J:134224]

Menet JS; Pescatore S; Rosbash M. 2014. CLOCK:BMAL1 is a pioneer-like transcription factor. Genes Dev 28(1):8-13. [PubMed: 24395244]  [MGI Ref ID J:205584]

Mistlberger RE; Yamazaki S; Pendergast JS; Landry GJ; Takumi T; Nakamura W. 2008. Comment on 'Differential rescue of light- and food-entrainable circadian rhythms'. Science 322(5902):675; author reply 675. [PubMed: 18974333]  [MGI Ref ID J:140633]

Musiek ES; Lim MM; Yang G; Bauer AQ; Qi L; Lee Y; Roh JH; Ortiz-Gonzalez X; Dearborn JT; Culver JP; Herzog ED; Hogenesch JB; Wozniak DF; Dikranian K; Giasson BI; Weaver DR; Holtzman DM; Fitzgerald GA. 2013. Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration. J Clin Invest 123(12):5389-400. [PubMed: 24270424]  [MGI Ref ID J:207831]

Owens L; Buhr E; Tu DC; Lamprecht TL; Lee J; Van Gelder RN. 2012. Effect of circadian clock gene mutations on nonvisual photoreception in the mouse. Invest Ophthalmol Vis Sci 53(1):454-60. [PubMed: 22159024]  [MGI Ref ID J:191526]

Peek CB; Affinati AH; Ramsey KM; Kuo HY; Yu W; Sena LA; Ilkayeva O; Marcheva B; Kobayashi Y; Omura C; Levine DC; Bacsik DJ; Gius D; Newgard CB; Goetzman E; Chandel NS; Denu JM; Mrksich M; Bass J. 2013. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342(6158):1243417. [PubMed: 24051248]  [MGI Ref ID J:202833]

Pendergast JS; Nakamura W; Friday RC; Hatanaka F; Takumi T; Yamazaki S. 2009. Robust food anticipatory activity in BMAL1-deficient mice. PLoS ONE 4(3):e4860. [PubMed: 19300505]  [MGI Ref ID J:147467]

Peruquetti RL; de Mateo S; Sassone-Corsi P. 2012. Circadian proteins CLOCK and BMAL1 in the chromatoid body, a RNA processing granule of male germ cells. PLoS One 7(8):e42695. [PubMed: 22900038]  [MGI Ref ID J:189932]

Pfeffer M; Muller CM; Mordel J; Meissl H; Ansari N; Deller T; Korf HW; von Gall C. 2009. The mammalian molecular clockwork controls rhythmic expression of its own input pathway components. J Neurosci 29(19):6114-23. [PubMed: 19439589]  [MGI Ref ID J:148758]

Ratajczak CK; Boehle KL; Muglia LJ. 2009. Impaired steroidogenesis and implantation failure in Bmal1-/- mice. Endocrinology 150(4):1879-85. [PubMed: 19056819]  [MGI Ref ID J:151819]

Reale ME; Webb IC; Wang X; Baltazar RM; Coolen LM; Lehman MN. 2013. The transcription factor Runx2 is under circadian control in the suprachiasmatic nucleus and functions in the control of rhythmic behavior. PLoS One 8(1):e54317. [PubMed: 23372705]  [MGI Ref ID J:195796]

Rudic RD; McNamara P; Curtis AM; Boston RC; Panda S; Hogenesch JB; Fitzgerald GA. 2004. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol 2(11):e377. [PubMed: 15523558]  [MGI Ref ID J:131694]

Scoma HD; Humby M; Yadav G; Zhang Q; Fogerty J; Besharse JC. 2011. The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork and regulates its sensitivity to light. PLoS One 6(9):e25382. [PubMed: 21966515]  [MGI Ref ID J:177916]

Shi G; Xing L; Liu Z; Qu Z; Wu X; Dong Z; Wang X; Gao X; Huang M; Yan J; Yang L; Liu Y; Ptacek LJ; Xu Y. 2013. Dual roles of FBXL3 in the mammalian circadian feedback loops are important for period determination and robustness of the clock. Proc Natl Acad Sci U S A 110(12):4750-5. [PubMed: 23471982]  [MGI Ref ID J:194250]

Shi SQ; Ansari TS; McGuinness OP; Wasserman DH; Johnson CH. 2013. Circadian disruption leads to insulin resistance and obesity. Curr Biol 23(5):372-81. [PubMed: 23434278]  [MGI Ref ID J:199735]

Shimba S; Ishii N; Ohta Y; Ohno T; Watabe Y; Hayashi M; Wada T; Aoyagi T; Tezuka M. 2005. Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis. Proc Natl Acad Sci U S A 102(34):12071-6. [PubMed: 16093318]  [MGI Ref ID J:101184]

Shostak A; Meyer-Kovac J; Oster H. 2013. Circadian regulation of lipid mobilization in white adipose tissues. Diabetes 62(7):2195-203. [PubMed: 23434933]  [MGI Ref ID J:208543]

Storch KF; Paz C; Signorovitch J; Raviola E; Pawlyk B; Li T; Weitz CJ. 2007. Intrinsic circadian clock of the Mammalian retina: importance for retinal processing of visual information. Cell 130(4):730-41. [PubMed: 17719549]  [MGI Ref ID J:124157]

Sun Y; Yang Z; Niu Z; Peng J; Li Q; Xiong W; Langnas AN; Ma MY; Zhao Y. 2006. MOP3, a component of the molecular clock, regulates the development of B cells. Immunology 119(4):451-60. [PubMed: 16925591]  [MGI Ref ID J:118522]

Sun Y; Yang Z; Niu Z; Wang W; Peng J; Li Q; Ma MY; Zhao Y. 2006. The mortality of MOP3 deficient mice with a systemic functional failure. J Biomed Sci 13(6):845-51. [PubMed: 16944268]  [MGI Ref ID J:135933]

Takasu NN; Kurosawa G; Tokuda IT; Mochizuki A; Todo T; Nakamura W. 2012. Circadian regulation of food-anticipatory activity in molecular clock-deficient mice. PLoS One 7(11):e48892. [PubMed: 23145013]  [MGI Ref ID J:195353]

Wang TA; Yu YV; Govindaiah G; Ye X; Artinian L; Coleman TP; Sweedler JV; Cox CL; Gillette MU. 2012. Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons. Science 337(6096):839-42. [PubMed: 22859819]  [MGI Ref ID J:186622]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB27

Colony Maintenance

Breeding & HusbandryWhen maintained as a live colony, hetetozygotes may be bred. It is recommended that females be disturbed as little as possible because they are prone to killing their litters. Homozygotes are viable, but both males and females are reportedly sterile.
Mating System+/+ sibling x Heterozygote         (Female x Male)   09-JUN-09
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $239.00Female or MaleHeterozygous for Arntltm1Bra  
Price per Pair (US dollars $)Pair Genotype
$311.00Heterozygous for Arntltm1Bra x Wild-type for Arntltm1Bra  
$311.00Wild-type for Arntltm1Bra x Heterozygous for Arntltm1Bra  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $310.70Female or MaleHeterozygous for Arntltm1Bra  
Price per Pair (US dollars $)Pair Genotype
$404.30Heterozygous for Arntltm1Bra x Wild-type for Arntltm1Bra  
$404.30Wild-type for Arntltm1Bra x Heterozygous for Arntltm1Bra  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
Ordering Information
JAX® Mice
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JAX® Services
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Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
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Terms of Use

Terms of Use


General Terms and Conditions


Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


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