Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Heterozygote         (Female x Male) Species laboratory mouse Generation N8+N1+F2 (10-DEC-07)   Donating Investigator Marie Demay,   Massachusetts General Hospital

Description
Heterozygous mice are phenotypically indistinguishable from wildtype siblings. Homozygous mice are viable and fertile with normal survival until approximately 14 months. RNA isolated from the intestine and kidney show a truncated deletion of the second zinc finger coding region followed by a premature termination codon, resulting in the absence of receptor protein. Homozygous mice exhibit an identical phenotype as the human disease hereditary vitamin D-dependent rickets type II (HVDDR). As early as 21 days of age, mutant mice demonstrate hypocalcemia, hypophosphatemia, hyperparathyroidism, increased serum parathyroid hormone, abnormal blood mineral levels, and growth retardation. In addition, renin and plasma angiotensin II levels are increased. Homozygous mice are hypertensive and exhibit cardiachypertrophy. At 4 weeks of age, homozygous mice exhibit perioral and periorbital alopecia that progresses over the entire body by 4 months of age. Rickets and osteomalacia develop by 35 days. Homozygous mice have increased bone fragility and other skeletal abnormalities. Introducing a diet enriched for calcium, phosphorus, and lactose, to young homozygous mice prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia. Lymphocytes isolated from homozygous mice have an inflammatory phenotype. Null mice have increased susceptibility to induced inflammatory bowel disease. Mutant mice may be useful in studies of rickets, alopecia, skeletal homeostasis, intestinal absorption, and inflammatory bowel disease.

Development
A targeting vector containing a mouse phosphoglycerate kinase promoter driven neomycin resistance gene was used to replace exon 3 of the endogenous gene. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric mice were bred to C57BL/6 to generate mutant colonies. Heterozygotes were mated to C57BL/6 mice for more than 8 generations before arriving at The Jackson Laboratory.

Control Information

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

Related Strains

Strains carrying other alleles of Vdr

006956

NOD.Cg-Vdrtm1Ska/CmatJ

View Strains carrying other alleles of Vdr     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Vitamin D-Dependent Rickets, Type II - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Vdr^tm1Mbd/Vdr⁺

        involves: 129S4/SvJae * C57BL/6

• cardiovascular system phenotype
• *normal* cardiovascular system phenotype (MGI Ref ID J:120353)
  • plasma levels of angiotensin II or aldosterone are not different from wild-type
  • ECG analysis does not reveal any significant differences from wild-type at 3, 6, or 9 months
• increased heart weight (MGI Ref ID J:120353)
  • heart weight to body weight ratio is increased 14% relative to wild-type

Vdr^tm1Mbd/Vdr^tm1Mbd

        involves: 129S4/SvJae

• endocrine/exocrine gland phenotype
• enlarged parathyroid gland (MGI Ref ID J:42815)
  • more than 10-fold increase in parathyroid gland size of 70-day-old mice
• growth/size phenotype
• decreased body weight (MGI Ref ID J:42815)
  • weigh 10% less than controls by 91 days of age; weight is normal at birth
• postnatal growth retardation (MGI Ref ID J:42815)
  • from 24 days of age, fail to grow as rapidly as controls
• homeostasis/metabolism phenotype
• hypocalcemia (MGI Ref ID J:42815)
  • become progressively hypocalcemic after day 21, maintaining ionized calcium levels about 25% lower than controls
  • blood ionized calcium levels are decreased by 30%
  • treatment with HCa-Lac (calcium, phosphorus, lactose) diet for 5 weeks normalizes calcium levels
• increased circulating angiotensinogen level (MGI Ref ID J:78067)
  • plasma angiotensinogen II levels are increased more than 2.5 fold compared to wildtype, however, expression of angiotensinogen is the same as wildtype
  • on a high salt (8%) diet, plasma angiotensinogen II levels are significantly increased over treated control
  • plasma angiotensinogen II levels are increased following 24 hour dehydration, however, levels for treated control exhibit a comparatively higher increase
• increased circulating parathyroid hormone level (MGI Ref ID J:63291)
  • starting on day 21, exhibit a progressive increase in parathyroid hormone levels
  • serum PTH concentration is increased 150-fold by 3 months of age
  • treatment with HCa-Lac (calcium, phosphorus, lactose) diet for 5 weeks lowers PTH concentration to 7-fold higher than control
• increased circulating renin level (MGI Ref ID J:78067)
  • renin is increased in the afferent glomerular arterioles as determined by immunoreactivity
• increased renin activity (MGI Ref ID J:78067)
  • circulating levels of angiotensin II are higher but liver levels of the angiotensinogen precursor are normal suggesting increased rennin activity
• increased urine potassium level (MGI Ref ID J:78067)
  • mice excrete 19% more potassium in urine, however, blood potassium concentration is normal
• increased urine sodium level (MGI Ref ID J:78067)
  • mice excrete 37% more sodium in urine, however, blood sodium concentration is normal
• skin/coat/nails phenotype
• alopecia (MGI Ref ID J:42815)
  • at 4 weeks of age, begin to develop perioral and periorbital alopecia
  • hair loss progresses to the entire body over the next 3 months, with more rapid progression in females than males
• dermal cysts (MGI Ref ID J:42815)
• distended hair follicles (MGI Ref ID J:42815)
• skeleton phenotype
• abnormal bone mineralization (MGI Ref ID J:42815)
  • decreased bone mineralization in 35 day old mice but not 15 day old mice
• rickets (MGI Ref ID J:42815)
• abnormal tibia morphology (MGI Ref ID J:42815)
  • decreased cortical width along the diaphysis and expansion and flaring of the growth plate at 35 days of age
• short tibia (MGI Ref ID J:42815)
  • tibias are about 15% shorter
• disorganized long bone epiphyseal plate (MGI Ref ID J:42815)
  • 35 day old growth plate is disorganized with an increase in vascularity and matrix
• increased width of hypertrophic chondrocyte zone (MGI Ref ID J:42815)
  • 15% increase in the number of hypertrophic chondrocytes per column in the tibia and vertebra of 15 day old mice and increased hypertrophic chondrocyte zone in 35 day old growth plate
• short femur (MGI Ref ID J:42815)
  • femurs are about 15% shorter
• limbs/digits/tail phenotype
• abnormal tibia morphology (MGI Ref ID J:42815)
  • decreased cortical width along the diaphysis and expansion and flaring of the growth plate at 35 days of age
• short tibia (MGI Ref ID J:42815)
  • tibias are about 15% shorter
• short femur (MGI Ref ID J:42815)
  • femurs are about 15% shorter
• behavior/neurological phenotype
• increased drinking behavior (MGI Ref ID J:78067)
  • mice drink approximately twice as much water as controls, however, glucose and insulin levels are normal
• cardiovascular system phenotype
• hypertension (MGI Ref ID J:78067)
  • mice are hypertensive with high systolic and the diastolic blood pressures caused in part by high circulating levels of renin and angiotensin II
• increased diastolic blood pressure (MGI Ref ID J:78067)
  • diastolic blood pressure is significantly higher (>20 mmHg) than those of wild-type littermates
• increased heart weight (MGI Ref ID J:78067)
  • heart weight to body weight ratio is significantly higher than control
• increased systolic blood pressure (MGI Ref ID J:78067)
  • systolic blood pressure is significantly higher (>20 mmHg) than those of wild-type littermates
• renal/urinary system phenotype
• increased urine potassium level (MGI Ref ID J:78067)
  • mice excrete 19% more potassium in urine, however, blood potassium concentration is normal
• increased urine sodium level (MGI Ref ID J:78067)
  • mice excrete 37% more sodium in urine, however, blood sodium concentration is normal
• polyuria (MGI Ref ID J:78067)

Vdr^tm1Mbd/Vdr^tm1Mbd

        involves: 129S4/SvJae * C57BL/6J

• homeostasis/metabolism phenotype
• abnormal mineral homeostasis (MGI Ref ID J:99866)
• hypophosphatemia (MGI Ref ID J:99866)
• skeleton phenotype
• abnormal chondrocyte morphology (MGI Ref ID J:99866)
  • impaired hypertrophic chondrocyte apoptosis
  • a 'rescue diet' of high-calcium/low-phosphate restores the normal level of apoptosis and the growth plate phenotype
• increased width of hypertrophic chondrocyte zone (MGI Ref ID J:99866)
  • expansion of the growth plate is associated with impaired apoptosis of late hypertrophic chondrocytes
• rickets (MGI Ref ID J:99866)
  • mutants develop rickets secondary to impaired apoptosis of late hypertrophic chondrocytes

Vdr^tm1Mbd/Vdr^tm1Mbd

        involves: 129S4/SvJae * C57BL/6

• life span-post-weaning/aging
• abnormal induced morbidity/mortality (MGI Ref ID J:130511)
  • up to 70% of mutants treated with DSS to induce colitis die within 2 weeks, compared to no mortality in treated wild-type
• growth/size phenotype
• weight loss (MGI Ref ID J:130511)
  • mice treated with 2.5% DSS lose up to 15% of body weight within 8 days after treatment, compared to almost no weight loss in treated wild-type
• digestive/alimentary phenotype
• abnormal intestinal epithelium morphology (MGI Ref ID J:130511)
  • severely distrupted and opened tight junctions and desmosomes are seen in colonic epithelia of DSS-treated mutants; in treated wild-type, epithelia appear normal
• abnormal intestinal mucosa morphology (MGI Ref ID J:130511)
  • erosions of mucosa of colon are observed on day 3 with 2.5% DSS treatment and substantial ulcerations are seen by day 7, while wild-type mice show no or some focal damage to mucosa on day 3 and day 7
  • in mice treated with 2% DSS for 2 or 3 days, transepithelial electrical resistance (TER) is significantly reduced even in absence of clinical symptoms of colitis, compared to controls, indicating impaired mucosal barrier integrity
• abnormal large intestine crypts of Lieberkuhn morphology (MGI Ref ID J:130511)
  • in some colon segments, ulceration is so severe that entire crypt structure is lost
  • no new crypts form around ulcers in mutants
• intestinal ulcer (MGI Ref ID J:130511)
  • severe ulceration is seen on day 7 of treatment for 7 days
  • by day 10, some epithelial cells appear to cover ulcerations, but very little cell proliferation or healing is seen compared to wild-type mice which show healing and reepithelization of ulcers with new crypts forming around ulcers at equivalent time point
• intestinal inflammation (MGI Ref ID J:107077)
  • spontaneous inflammatory bowel disease (IBD) develops
• increased susceptibility to induced colitis (MGI Ref ID J:130511)
  • mice treated with 2.5% dextran sodium sulfate (DSS) for 1 week show more severe colitis development than treated wild-type
• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:107077)
  • at 5 weeks, thymi are not different than in wild-type
• abnormal interleukin level (MGI Ref ID J:107077)
  • Il-1beta is expressed in the colon; older mutants (>9 months) display 10-fold higher levels than younger mice, whereas wild-type controls do not express any cytokines in the colon at any age
• abnormal tumor necrosis factor level (MGI Ref ID J:107077)
  • low levels of expression are detected in colons of young animals, and levels are 20-fold higher in older mice (>9 months)
• increased thymus weight (MGI Ref ID J:107077)
  • increases with time and IBD
• intestinal inflammation (MGI Ref ID J:107077)
  • spontaneous inflammatory bowel disease (IBD) develops
• increased susceptibility to induced colitis (MGI Ref ID J:130511)
  • mice treated with 2.5% dextran sodium sulfate (DSS) for 1 week show more severe colitis development than treated wild-type
• thymus hyperplasia (MGI Ref ID J:107077)
  • increases with time and IBD
• hematopoietic system phenotype
• increased thymus weight (MGI Ref ID J:107077)
  • increases with time and IBD
• thymus hyperplasia (MGI Ref ID J:107077)
  • increases with time and IBD
• cardiovascular system phenotype
• *normal* cardiovascular system phenotype (MGI Ref ID J:120353)
  • plasma levels of angiotensin II or aldosterone are not different from wild-type
  • ECG analysis does not reveal any significant differences from wild-type at 3, 6, or 9 months
• abnormal myocardial fiber physiology (MGI Ref ID J:131143)
• cardiac fibrosis (MGI Ref ID J:120340)
  • heart tissue displays increased collagen deposition primarily in the extracellular matrix
• cardiac hypertrophy (MGI Ref ID J:120340)
  • heart tissue displays increased cell size
• decreased systolic blood pressure (MGI Ref ID J:120353)
  • at 9 months, pressure is significantly lower than in wild-type
• increased heart weight (MGI Ref ID J:120353)
  • heart weight to body weight ratio is increased 41% relative to wild-type
  • heart weight to body weight ratio is increased to 6.9 from 4.9 in wild-type at 12 months
• endocrine/exocrine gland phenotype
• abnormal large intestine crypts of Lieberkuhn morphology (MGI Ref ID J:130511)
  • in some colon segments, ulceration is so severe that entire crypt structure is lost
  • no new crypts form around ulcers in mutants
• homeostasis/metabolism phenotype
• abnormal enzyme/coenzyme activity (MGI Ref ID J:120340)
  • matrix metalloproteinase-2 and -9 activities in heart tissue (ventricular) are increased relative to wild-type
• abnormal renin activity (MGI Ref ID J:120353)
  • plasma renin activity is increased by 50% but difference from wild-type activity is not significant
• abnormal interleukin level (MGI Ref ID J:107077)
  • Il-1beta is expressed in the colon; older mutants (>9 months) display 10-fold higher levels than younger mice, whereas wild-type controls do not express any cytokines in the colon at any age
• abnormal tumor necrosis factor level (MGI Ref ID J:107077)
  • low levels of expression are detected in colons of young animals, and levels are 20-fold higher in older mice (>9 months)

View Research Applications

Research Applications

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

Cardiovascular Research
Other

Dermatology Research
Skin and Hair Texture Defects

Endocrine Deficiency Research
Bone/Bone Marrow Defects
Gastrointestinal Defects
Skin Defects

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines
Immunodeficiency (Inflammatory bowel disease)
Inflammation (Inflammatory bowel disease)

Internal/Organ Research
Gastrointestinal Defects (colitis)
Kidney Defects

Vdr^tm1Mbd related

Cardiovascular Research
Other

Dermatology Research
Skin and Hair Texture Defects

Endocrine Deficiency Research
Bone/Bone Marrow Defects
Gastrointestinal Defects
Skin Defects

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines
Immunodeficiency (Inflammatory bowel disease)
Inflammation (Inflammatory bowel disease)

Internal/Organ Research
Gastrointestinal Defects (colitis)
Kidney Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Vdrtm1Mbd
Allele Name		targeted mutation 1, Marie B Demay
Allele Type		Targeted (knock-out)
Common Name(s)		VDR -; VDR-KO;
Mutation Made By		Marie Demay,   Massachusetts General Hospital
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Vdr, vitamin D receptor
Chromosome		15
Gene Common Name(s)		NR1I1;
Molecular Note		A 5 kb region of the gene encompassing exon 3 was replaced with a PGK-neo cassette via homologous recombination resulting in deletion of the second zinc finger of the DNA-binding domain. RT-PCR analysis of intestines and kidneys from homozygous mutant animals detected a mutant transcript. Sequence analysis revealed a 131 bp deletion corresponding to the second zinc finger and results in a frameshift and nonsense codon 12 bp downstream. [MGI Ref ID J:42815]

Genotyping

Genotyping Information

Genotyping Protocols

Vdr^tm1Mbd, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Vdr^tm1Mbd related

Amling M; Priemel M; Holzmann T; Chapin K; Rueger JM; Baron R; Demay MB. 1999. Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: formal histomorphometric and biomechanical analyses. Endocrinology 140(11):4982-7. [PubMed: 10537122]  [MGI Ref ID J:114167]

Bolt MJ; Liu W; Qiao G; Kong J; Zheng W; Krausz T; Cs-Szabo G; Sitrin MD; Li YC. 2004. Critical role of vitamin D in sulfate homeostasis: regulation of the sodium-sulfate cotransporter by 1,25-dihydroxyvitamin D3. Am J Physiol Endocrinol Metab 287(4):E744-9. [PubMed: 15165995]  [MGI Ref ID J:95405]

Chen CH; Sakai Y; Demay MB. 2001. Targeting expression of the human vitamin D receptor to the keratinocytes of vitamin D receptor null mice prevents alopecia. Endocrinology 142(12):5386-9. [PubMed: 11713240]  [MGI Ref ID J:108797]

Demay MB; MacDonald PN; Skorija K; Dowd DR; Cianferotti L; Cox M. 2007. Role of the vitamin D receptor in hair follicle biology. J Steroid Biochem Mol Biol 103(3-5):344-6. [PubMed: 17223342]  [MGI Ref ID J:120248]

Froicu M; Zhu Y; Cantorna MT. 2006. Vitamin D receptor is required to control gastrointestinal immunity in IL-10 knockout mice. Immunology 117(3):310-8. [PubMed: 16476050]  [MGI Ref ID J:107077]

Goltzman D. 2007. Use of genetically modified mice to examine the skeletal anabolic activity of vitamin D. J Steroid Biochem Mol Biol 103(3-5):587-91. [PubMed: 17254773]  [MGI Ref ID J:120278]

Gunther T; Chen ZF; Kim J; Priemel M; Rueger JM; Amling M; Moseley JM; Martin TJ; Anderson DJ; Karsenty G. 2000. Genetic ablation of parathyroid glands reveals another source of parathyroid hormone. Nature 406(6792):199-203. [PubMed: 10910362]  [MGI Ref ID J:63291]

Guzey M; Jukic D; Arlotti J; Acquafondata M; Dhir R; Getzenberg RH. 2004. Increased apoptosis of periprostatic adipose tissue in VDR null mice. J Cell Biochem 93(1):133-41. [PubMed: 15352170]  [MGI Ref ID J:92877]

Kong J; Grando SA; Li YC. 2006. Regulation of IL-1 family cytokines IL-1alpha, IL-1 receptor antagonist, and IL-18 by 1,25-dihydroxyvitamin D3 in primary keratinocytes. J Immunol 176(6):3780-7. [PubMed: 16517748]  [MGI Ref ID J:129534]

Kong J; Zhang Z; Musch MW; Ning G; Sun J; Hart J; Bissonnette M; Li YC. 2008. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol 294(1):G208-16. [PubMed: 17962355]  [MGI Ref ID J:130511]

Kovacs CS; Woodland ML; Fudge NJ; Friel JK. 2005. The vitamin D receptor is not required for fetal mineral homeostasis or for the regulation of placental calcium transfer in mice. Am J Physiol Endocrinol Metab 289(1):E133-44. [PubMed: 15741244]  [MGI Ref ID J:99514]

Li YC; Bolt MJ; Cao LP; Sitrin MD. 2001. Effects of vitamin D receptor inactivation on the expression of calbindins and calcium metabolism. Am J Physiol Endocrinol Metab 281(3):E558-64. [PubMed: 11500311]  [MGI Ref ID J:107742]

Li YC; Kong J; Wei M; Chen ZF; Liu SQ; Cao LP. 2002. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 110(2):229-38. [PubMed: 12122115]  [MGI Ref ID J:78067]

Li YC; Pirro AE; Amling M; Delling G; Baron R; Bronson R; Demay MB. 1997. Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia. Proc Natl Acad Sci U S A 94(18):9831-5. [PubMed: 9275211]  [MGI Ref ID J:42815]

Li YC; Pirro AE; Demay MB. 1998. Analysis of vitamin D-dependent calcium-binding protein messenger ribonucleic acid expression in mice lacking the vitamin D receptor. Endocrinology 139(3):847-51. [PubMed: 9492012]  [MGI Ref ID J:114263]

Marks HD; Fleet JC; Peleg S. 2007. Transgenic expression of the human Vitamin D receptor (hVDR) in the duodenum of VDR-null mice attenuates the age-dependent decline in calcium absorption. J Steroid Biochem Mol Biol 103(3-5):513-6. [PubMed: 17207992]  [MGI Ref ID J:120281]

Panda DK; Miao D; Bolivar I; Li J; Huo R; Hendy GN; Goltzman D. 2004. Inactivation of the 25-hydroxyvitamin D 1alpha-hydroxylase and vitamin D receptor demonstrates independent and interdependent effects of calcium and vitamin D on skeletal and mineral homeostasis. J Biol Chem 279(16):16754-66. [PubMed: 14739296]  [MGI Ref ID J:89533]

Rahman A; Hershey S; Ahmed S; Nibbelink K; Simpson RU. 2007. Heart extracellular matrix gene expression profile in the vitamin D receptor knockout mice. J Steroid Biochem Mol Biol 103(3-5):416-9. [PubMed: 17275288]  [MGI Ref ID J:120340]

Sabbagh Y; Carpenter TO; Demay MB. 2005. Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. Proc Natl Acad Sci U S A 102(27):9637-42. [PubMed: 15976027]  [MGI Ref ID J:99866]

Sakai Y; Demay MB. 2000. Evaluation of keratinocyte proliferation and differentiation in vitamin D receptor knockout mice. Endocrinology 141(6):2043-9. [PubMed: 10830288]  [MGI Ref ID J:108817]

Sakai Y; Kishimoto J; Demay MB. 2001. Metabolic and cellular analysis of alopecia in vitamin D receptor knockout mice. J Clin Invest 107(8):961-6. [PubMed: 11306599]  [MGI Ref ID J:68883]

Simpson RU; Hershey SH; Nibbelink KA. 2007. Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse. J Steroid Biochem Mol Biol 103(3-5):521-4. [PubMed: 17275289]  [MGI Ref ID J:120353]

Skorija K; Cox M; Sisk JM; Dowd DR; Macdonald PN; Thompson CC; Demay MB. 2005. Ligand-independent actions of the vitamin d receptor maintain hair follicle homeostasis. Mol Endocrinol 19(4):855-62. [PubMed: 15591533]  [MGI Ref ID J:96966]

St-Arnaud R; Arabian A; Travers R; Barletta F; Raval-Pandya M; Chapin K; Depovere J; Mathieu C; Christakos S; Demay MB; Glorieux FH. 2000. Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is due to elevated 1,25-dihydroxyvitamin D and not to the absence of 24,25-dihydroxyvitamin D. Endocrinology 141(7):2658-66. [PubMed: 10875271]  [MGI Ref ID J:63457]

Tishkoff DX; Nibbelink KA; Holmberg KH; Dandu L; Simpson RU. 2008. Functional vitamin D receptor (VDR) in the t-tubules of cardiac myocytes: VDR knockout cardiomyocyte contractility. Endocrinology 149(2):558-64. [PubMed: 17974622]  [MGI Ref ID J:131143]

Welsh J; Wietzke JA; Zinser GM; Smyczek S; Romu S; Tribble E; Welsh JC; Byrne B; Narvaez CJ. 2003. Impact of the Vitamin D3 receptor on growth-regulatory pathways in mammary gland and breast cancer. J Steroid Biochem Mol Biol 83(1-5):85-92. [PubMed: 12650704]  [MGI Ref ID J:82977]

Xiang W; Kong J; Chen S; Cao LP; Qiao G; Zheng W; Liu W; Li X; Gardner DG; Li YC. 2005. Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab 288(1):E125-32. [PubMed: 15367398]  [MGI Ref ID J:96045]

Yu S; Cantorna MT. 2008. The vitamin D receptor is required for iNKT cell development. Proc Natl Acad Sci U S A 105(13):5207-12. [PubMed: 18364394]  [MGI Ref ID J:133570]

Yu X; Sabbagh Y; Davis SI; Demay MB; White KE. 2005. Genetic dissection of phosphate- and vitamin D-mediated regulation of circulating Fgf23 concentrations. Bone 36(6):971-7. [PubMed: 15869926]  [MGI Ref ID J:123814]

Zheng W; Xie Y; Li G; Kong J; Feng JQ; Li YC. 2004. Critical role of calbindin-D28k in calcium homeostasis revealed by mice lacking both vitamin D receptor and calbindin-D28k. J Biol Chem 279(50):52406-13. [PubMed: 15456794]  [MGI Ref ID J:95170]

Zhu Y; Mahon BD; Froicu M; Cantorna MT. 2005. Calcium and 1 alpha,25-dihydroxyvitamin D3 target the TNF-alpha pathway to suppress experimental inflammatory bowel disease. Eur J Immunol 35(1):217-24. [PubMed: 15593122]  [MGI Ref ID J:95228]

Zinser G; Packman K; Welsh J. 2002. Vitamin D(3) receptor ablation alters mammary gland morphogenesis. Development 129(13):3067-76. [PubMed: 12070083]  [MGI Ref ID J:110843]

Zinser GM; Suckow M; Welsh J. 2005. Vitamin D receptor (VDR) ablation alters carcinogen-induced tumorigenesis in mammary gland, epidermis and lymphoid tissues. J Steroid Biochem Mol Biol 97(1-2):153-64. [PubMed: 16111884]  [MGI Ref ID J:102891]

Zinser GM; Sundberg JP; Welsh J. 2002. Vitamin D(3) receptor ablation sensitizes skin to chemically induced tumorigenesis. Carcinogenesis 23(12):2103-9. [PubMed: 12507934]  [MGI Ref ID J:81031]

Zinser GM; Welsh J. 2004. Accelerated Mammary Gland Development during Pregnancy and Delayed Postlactational Involution in Vitamin D3 Receptor Null Mice. Mol Endocrinol 18(9):2208-23. [PubMed: 15178742]  [MGI Ref ID J:92080]

Zinser GM; Welsh J. 2004. Vitamin D receptor status alters mammary gland morphology and tumorigenesis in MMTV-neu mice. Carcinogenesis 25(12):2361-72. [PubMed: 15333467]  [MGI Ref ID J:94402]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony on a C57BL/6 background, mutant mice can be bred as heterozygotes or homozygotes, but homozygous mice rarely have multiple litters. Fertility of young homozygous mice is increased by placing them on a diet enriched for calcium, phosphorus, and lactose.
Mating System	Heterozygote x Heterozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.