Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation B6N2F7+N1   Donating Investigator Nobuyo Maeda,   Univ of North Carolina at Chapel Hill

Appearance
black
Related Genotype: a/a

Description
Mice deficient in cystathionine-beta synthase suffer from severe growth retardation and a majority of them are dead by 5 weeks of age. Histological examination showed that the hepatocytes of homozygotes were enlarged, multinucleated, and filled with microvesicular lipid droplets. Plasma homocysteine levels of the homozygotes were approximately 40 times normal. Homozygotes may be used as a model for severe homocysteinemia. Heterozygous mutants have an approximately 50% reduction in cystathionine beta-synthase mRNA and enzyme activity in the liver and have twice normal plasma homocysteine levels. Thus, the heterozygous mutants are promising for studying the in vivo role of elevated levels of homocysteine in the etiology of cardiovascular diseases.

Development
The Cbs-deficient strain was developed in the lab of Dr. Nobuyo Maeda at The University of North Carolina at Chapel Hill. The 129/Ola-derived BK4 ES cell line was used.

Control Information

	Control
	Wild-type from the colony
	100903 B6129PF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Cbs^tm1Unc allele

002853

B6.129P2-Cbstm1Unc/J

View Strains carrying   Cbs^tm1Unc     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

	Homocysteinemia - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
	Homocysteinemia - 5
	Homocystinuria - 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). 5 Conditionally targeted allele(s)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Cbs^tm1Unc/Cbs⁺

        involves: 129P2/OlaHsd * C57BL/6J

• homeostasis/metabolism phenotype
• abnormal circulating homocysteine level (MGI Ref ID J:23321)
  • at P21, heterozygotes show a 2-fold increase in plasma homocysteine levels relative to wild-type mice
  • homocysteine concentrations decrease with age in wild-type and heterozygous mice, reaching levels of 3 nmol/ml and 7 nmol/ml, respectively, by 22 weeks of age
• liver/biliary system phenotype
• abnormal hepatocyte morphology (MGI Ref ID J:23321)
  • hepatocytes have anisonucleosis and fairly prominent nucleoli and appear to be slightly larger
• skin/coat/nails phenotype
• *normal* skin/coat/nails phenotype (MGI Ref ID J:105571)
  • at 3 months, heterozygotes display normal skin and hair morphology

Cbs^tm1Unc/Cbs^tm1Unc

        involves: 129P2/OlaHsd * C57BL/6J

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:23321)
  • homozygotes are present at roughly the expected Mendelian frequency until P14; however, less than 60% of the expected number of homozygotes are obtained at 3 weeks of age
• life span-post-weaning/aging
• premature death (MGI Ref ID J:101303)
  • on a standard laboratory diet, homozygotes show a high incidence of lethality between 3 and 4 weeks after birth, with the majority dying within 5 weeks of age; only ~20% of the expected number is obtained at 5-12 weeks of age
  • dietary supplementation with choline at weaning extends postnatal survival to adulthood
• lethality-prenatal/perinatal
• lethality throughout fetal growth and development (MGI Ref ID J:114850)
  • despite a similar number of implantation sites, the percentage of surviving fetuses in homozygous pregnant females is severely reduced relative to wild-type pregnant females
• growth/size phenotype
• decreased body size (MGI Ref ID J:105571)
  • at P21, most homozygotes appear runted relative to wild-type mice
• decreased body weight (MGI Ref ID J:23321)
  • at P14, homozygotes display body weights that are only 80% of those found in wild-type or heterozygous mice
  • at 3 weeks, homozygotes weigh significantly less than wild-type mice
• postnatal growth retardation (MGI Ref ID J:23321)
  • homozygotes show a progressive failure in weight gain after P7; differences in body weight become pronounced between P14 and P21
  • a few homozygotes surviving >2 months display normal stature at weaning and maintain a relatively normal body size until just before death
  • on a choline-enriched diet, adult homozygotes exhibit growth retardation, weighing an average of 20% less than wild-type or heterozygous mice
• liver/biliary system phenotype
• abnormal hepatocyte morphology (MGI Ref ID J:23321)
  • at P14-P21, mutant hepatocytes appear enlarged and pleiomorphic, with a 2-fold increase in mean diameter and enlarged nuclei; multi- and binucleated hepatocytes are present
• increased hepatocyte apoptosis (MGI Ref ID J:101303)
  • at 8- and 12 weeks, mutant livers exhibit a significantly increased proapoptotic Bax/Bcl-2 ratio (up to 16 vs. 1 arbitrary unit), suggesting induction of a mitochondrial apoptotic pathway
  • however, no caspase-3 activation, DNA fragmentation, or TUNEL-positive cells are detected at 12 weeks or later, suggesting that protective signals may counteract apoptotic signals, leading to chronic inflammation
• enlarged liver (MGI Ref ID J:23321)
  • occasionally, older female homozygotes (one 3-mo-old and one 6-mo-old) show hepatomegaly with subtle autolyic changes
• hepatic steatosis (MGI Ref ID J:23321)
  • at P21, some mutant hepatocytes contain microvesicular cytoplasmic lipid droplets
  • on a standard laboratory diet, homozygotes develop hepatic steatosis at ~P15, with lipid droplets containing triacylglycerols and cholesteryl esters
  • on a choline-enriched diet, homozygotes exhibit a mild, localized hepatic steatosis (grade 1) at 12 and 18 weeks, which progresses to extensive grade 2 steatosis by 32 weeks of age
• liver fibrosis (MGI Ref ID J:101303)
  • on a standard laboratory diet, homozygotes develop hepatic fibrosis at ~P15
  • on a choline-enriched diet, 8-week-old homozygotes display a mild hepatic perivascular fibrosis which progresses to pericellular fibrosis at week 12 and portal fibrosis by week 32, along with a ~50-fold increase in liver collagen content
• liver inflammation (MGI Ref ID J:101303)
  • on a choline-enriched diet, 8-week-old and ageing homozygotes display mild hepatic inflammation, with foci of perilobular mononuclear inflammatory infiltrates around the vessels
  • however, no hepatocyte necrosis is detected up to 32 weeks age
• pale liver (MGI Ref ID J:23321)
  • at P21, mutant livers show a light tan color instead of a normal reddish-brown color
• homeostasis/metabolism phenotype
• abnormal circulating homocysteine level (MGI Ref ID J:23321)
  • at P21, F2 homozygotes show plasma homocysteine levels that are ~40 times higher than those of age-matched wild-type mice
  • at 3 months, homozygotes fed a choline-enriched diet, show a 50-fold increase in total plasma homocysteine levels relative to similarly fed wild-type mice
  • at 3 months, homozygotes show a 20-fold increase in mean hepatic homocysteine levels relative to wild-type mice
• abnormal interleukin level (MGI Ref ID J:101303)
  • at 8- and 12 weeks, mutant livers display significantly higher IL-6 mRNA levels relative to wild-type livers
• abnormal tumor necrosis factor level (MGI Ref ID J:101303)
  • at 8- and 12 weeks, mutant livers display significantly higher TNF mRNA levels relative to wild-type livers; CD14 mRNA levels are also increased, confirming Kuppfer cell activation and elevated TNF production
• hemosiderosis (MGI Ref ID J:23321)
  • at P21, one of 4 homozygotes display hemosiderin deposits in spleen
• increased circulating progesterone level (MGI Ref ID J:114850)
  • at day 6 after mating with vasectomized males, plasma progesterone levels are significantly higher in pseudo-pregnant female homozygotes relative to their wild-type counterparts
• hematopoietic system phenotype
• extramedullary hematopoiesis (MGI Ref ID J:23321)
  • at P21, mutant (but not wild-type) hepatocytes display extramedullary hematopoiesis
• limbs/digits/tail phenotype
• abnormal skeleton extremities morphology (MGI Ref ID J:23321)
  • homozygotes dying at early postnatal stages display tails and extremities of smaller diameters relative to their length
  • at P21, mutant knee joints appear immature relative to wild-type joints
• reproductive system phenotype
• abnormal ovarian follicle number (MGI Ref ID J:114850)
  • in response to the ovulatory surge of hCG, female homozygotes develop less follicles than wild-type females, indicating a reduced response to pregnant mare serum gonadotropin
  • in addition, superovulated female homozygotes display an increased Oil red O staining of lipids in the ovarian corpora lutea relative to wild-type females
• abnormal uterus weight (MGI Ref ID J:114850)
  • female homozygotes show a striking decrease in gravid uterine weight relative to wild-type females; this is accompanied by significant reductions in placental and fetal weights
  • notably, the endometrium, muscular layer and perimetrium appear histologically normal
• decreased litter size (MGI Ref ID J:114850)
  • matings between female x male homozygotes result in a drastic reduction of litter size, since five homozygous females had only two born pups, which died soon after birth, versus 39 obtained with heterozygous females
• female infertility (MGI Ref ID J:23321)
  • female homozygotes surviving >2months fail to reproduce
  • female homozygotes show normal sexual behavior but are infertile due to uterine failure
  • fertility is restored when homozygous mutant ovaries are transplanted to normal ovarectomized recipients
  • as both mutant ovaries and ovulated oocytes appear morphologically normal, authors suggest that uterine dysfunction is a consequence of either hyperhomocysteinemia or other factor(s) in the uterine environment of homozygous mutant females
• prolonged metestrous (MGI Ref ID J:114850)
• short diestrous (MGI Ref ID J:114850)
• short estrous cycle (MGI Ref ID J:114850)
  • infertile female homozygotes show a shorter and irregular estrus cycle
  • both estrus and diestrus periods are decreased while the metestrus is prolonged
  • differences in estrus cycle have no effect over the number of oocytes ovulated during normal estruses, although the yield is much lower when female homozygotes are superovulated
• short estrous (MGI Ref ID J:114850)
• vision/eye phenotype
• abnormal eye development (MGI Ref ID J:23321)
  • at P21, mutant eyes appear immature relative to wild-type or heterozygous eyes; however, no ocular pathology is observed
• delayed eyelid opening (MGI Ref ID J:23321)
  • homozygotes dying at early postnatal stages show delayed eyelid opening
• microphthalmia (MGI Ref ID J:23321)
  • at P21, most homozygotes exhibit smaller eyes
• skeleton phenotype
• abnormal skeleton extremities morphology (MGI Ref ID J:23321)
  • homozygotes dying at early postnatal stages display tails and extremities of smaller diameters relative to their length
  • at P21, mutant knee joints appear immature relative to wild-type joints
• respiratory system phenotype
• abnormal lung development (MGI Ref ID J:23321)
  • at P21, mutant lungs appear immature relative to wild-type or heterozygous lungs
• renal/urinary system phenotype
• delayed kidney development (MGI Ref ID J:23321)
  • at P21, mutant kidneys appear immature relative to wild-type or heterozygous kidneys
• cardiovascular system phenotype
• abnormal heart development (MGI Ref ID J:23321)
  • at P21, mutant hearts appear immature relative to wild-type or heterozygous hearts
  • no thrombi are detected in vascular segments or other tissues
• craniofacial phenotype
• abnormal facial morphology (MGI Ref ID J:23321)
  • homozygotes dying at early postnatal stages have faces that are typical of very young animals
• pointed snout (MGI Ref ID J:105571)
  • homozygotes display a pointed snout
• skin/coat/nails phenotype
• abnormal coat appearance (MGI Ref ID J:105571)
  • homozygotes lack a normal healthy fur; in contrast, vibrissae, eyelids and nails appear normal
• abnormal hair follicle morphology (MGI Ref ID J:105571)
  • at 3 months, mutant hair roots extend deeper into the subcutaneous fatty tissues while the basal portion of the follicles remains in the hypodermis
  • homozygotes exhibit an increased number of hair follicles on their backs
• abnormal hair growth (MGI Ref ID J:105571)
  • at 3 months, homozygotes exhibit a sparse fur on their head and a more dense fur on their backs
  • homozygotes display a variable reduction in the (mid-shaft) diameter of back, abdominal, and head hairs
• abnormal keratinocyte differentiation (MGI Ref ID J:105571)
  • at 3 months, homozygotes exhibit accelerated maturation of keratinocytes
• enlarged sebaceous gland (MGI Ref ID J:105571)
  • at 3 months, homozygotes exhibit hyperplastic sebaceous glands
• enlarged spinous cells (MGI Ref ID J:105571)
  • at 3 months, the mutant epidermis displays enlarged spinous cells, in the absence of increased proliferation
• hyperkeratosis (MGI Ref ID J:105571)
  • at 3 months, homozygotes epidermal hyperkeratosis
  • however, melanocyte morphology appears normal, and no changes in hair or skin color are observed
• thin dermal layer (MGI Ref ID J:105571)
  • at 3 months, homozygotes show a thin dermis; however, epidermal-dermal junctions appear normal
• thin hypodermis (MGI Ref ID J:105571)
  • at 3 months, homozygotes display a thinner hypodermis
• wrinkled skin (MGI Ref ID J:105571)
• endocrine/exocrine gland phenotype
• abnormal ovarian follicle number (MGI Ref ID J:114850)
  • in response to the ovulatory surge of hCG, female homozygotes develop less follicles than wild-type females, indicating a reduced response to pregnant mare serum gonadotropin
  • in addition, superovulated female homozygotes display an increased Oil red O staining of lipids in the ovarian corpora lutea relative to wild-type females
• enlarged sebaceous gland (MGI Ref ID J:105571)
  • at 3 months, homozygotes exhibit hyperplastic sebaceous glands
• cellular phenotype
• oxidative stress (MGI Ref ID J:101303)
  • at 3 months, mutant livers exhibit enhanced protein oxidation and lipid peroxidation, as shown by a ~30% increase in oxidatively modified proteins (carbonyls) and a similar increase in MDA and 4-HNE aldehydes, respectively
  • hepatic oxidative stress may cause mitochondrial damage in association with activation of hepatic Kuppfer (stellate) cells, leading to liver injury
• immune system phenotype
• abnormal interleukin level (MGI Ref ID J:101303)
  • at 8- and 12 weeks, mutant livers display significantly higher IL-6 mRNA levels relative to wild-type livers
• abnormal tumor necrosis factor level (MGI Ref ID J:101303)
  • at 8- and 12 weeks, mutant livers display significantly higher TNF mRNA levels relative to wild-type livers; CD14 mRNA levels are also increased, confirming Kuppfer cell activation and elevated TNF production
• liver inflammation (MGI Ref ID J:101303)
  • on a choline-enriched diet, 8-week-old and ageing homozygotes display mild hepatic inflammation, with foci of perilobular mononuclear inflammatory infiltrates around the vessels
  • however, no hepatocyte necrosis is detected up to 32 weeks age
• embryogenesis phenotype
• abnormal maternal decidual layer morphology (MGI Ref ID J:114850)
  • at day 18 of gestation, the thickness of decidual layer is reduced in placentas from pregnant female homozygotes, indicating reduced trophoblast invasion in these females
• abnormal placenta junctional zone morphology (MGI Ref ID J:114850)
  • at day 18 of gestation, the junctional zone is reduced in placentae of female homozygotes
• abnormal placenta labyrinth morphology (MGI Ref ID J:114850)
  • at day 18 of gestation, the labyrinthine zone is enlarged in placentae of female homozygotes
• decreased placenta weight (MGI Ref ID J:114850)
  • at day 18 of gestation, female homozygotes display a decrease of placental mass that correlates with the presence of weakened layers

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

Cbs^tm1Unc/Cbs⁺

        B6.129P2-Cbs^tm1Unc/J

• homeostasis/metabolism phenotype
• abnormal circulating homocysteine level (MGI Ref ID J:64885)
  • on a control diet, heterozygotes display normal plasma total homocysteine levels relative to wild-type mice (6.4 ± 0.6 µM vs 5.3 ± 0.7 µM, respectively)
  • however, on a low-folate diet, heterozygotes exhibit siginifcantly elevated plasma total homocysteine levels relative to wild-type mice (25.1 ± 3.2 µM vs 11.6 ± 4.5 µM, respectively)
• cardiovascular system phenotype
• abnormal vascular endothelial cell physiology (MGI Ref ID J:64885)
  • on a low-folate diet (~50% reduction in plasma folate levels), heterozygotes display a significant endothelial vasomotor dysfunction associated with moderate hyperhomocysteinemia
  • endothelial vasomotor dysfunction is noted only in mice with a combined defect in homocysteine remethylation (produced by dietary folate deficiency) and homocysteine transsulfuration (produced by heterozygous deficiency)
• abnormal vasodilation (MGI Ref ID J:64885)
  • on a control diet, heterozygotes show normal relaxation of aortic rings in response to the endothelium-dependent vasodilator acetylcholine relative to wild-type mice
  • however, on a low-folate diet, heterozygotes exhibit impaired maximal relaxation of aortic rings in response to acetylcholine relative to wild-type mice (58 ± 9% vs 84 ± 4%, respectively)
  • no significant differences in relaxation to nitroprusside or contraction to the thromboxane A2 analog U-46619 are observed between wild-type and heterozygous mice fed either control or low-folate diets
  • no significant differences in aortic thrombomodulin activity are observed between wild-type and heterozygous mice fed either control or low-folate diets

View Research Applications

Research Applications

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

Cbs^tm1Unc related

Internal/Organ Research
Liver Defects

Metabolism Research

Mouse/Human Gene Homologs
homocystinuria

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cbstm1Unc
Allele Name		targeted mutation 1, University of North Carolina
Allele Type		Targeted (knock-out)
Common Name(s)		CBS; CBS-;
Mutation Made By		Nobuyo Maeda,   Univ of North Carolina at Chapel Hill
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		BK4
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Cbs, cystathionine beta-synthase
Chromosome		17
Gene Common Name(s)		AI047524; AI303044; HIP4; MGC:18856; MGC:18895; MGC:37300; expressed sequence AI047524; expressed sequence AI303044;
General Note		Homozygotes may serve as models of severe homocysteinemia and increase our understanding of the pathophysiology of CBS deficiency, while the apparently healthy heterozygotes will elucidate the role of moderately increased homocysteine levels on the etiology of cardiovascular diseases (J:23321).
Molecular Note		A neomycin selection gene replaced a genomic fragment containing exons 3 and 4, which contains sequences encoding conserved residues thought to be required for protein activity. Northern blot analysis on mRNA derived from liver tissue of homozygous micedemonstrated that no stable transcript is produced from this allele. [MGI Ref ID J:23321]

Genotyping

Genotyping Information

Genotyping Protocols

Cbs^tm1unc, SEP PCR, vers. 2
Cbs^tm1unc, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Watanabe M; Osada J; Aratani Y; Kluckman K; Reddick R; Malinow MR; Maeda N. 1995. Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia. Proc Natl Acad Sci U S A 92(5):1585-9. [PubMed: 7878023]  [MGI Ref ID J:23321]

Additional References

Cbs^tm1Unc related

Akahoshi N; Kobayashi C; Ishizaki Y; Izumi T; Himi T; Suematsu M; Ishii I. 2008. Genetic background conversion ameliorates semi-lethality and permits behavioral analyses in cystathionine beta-synthase-deficient mice, an animal model for hyperhomocysteinemia. Hum Mol Genet 17(13):1994-2005. [PubMed: 18364386]  [MGI Ref ID J:136853]

Alberto JM; Hamelet J; Noll C; Blaise S; Bronowicki JP; Gueant JL; Delabar JM; Janel N. 2007. Mice deficient in cystathionine beta synthase display altered homocysteine remethylation pathway. Mol Genet Metab 91(4):396-8. [PubMed: 17562377]  [MGI Ref ID J:123017]

Baumbach GL; Sigmund CD; Bottiglieri T; Lentz SR. 2002. Structure of cerebral arterioles in cystathionine beta-synthase-deficient mice. Circ Res 91(10):931-7. [PubMed: 12433838]  [MGI Ref ID J:109002]

Choumenkovitch SF; Selhub J; Bagley PJ; Maeda N; Nadeau MR; Smith DE; Choi SW. 2002. In the cystathionine beta-synthase knockout mouse, elevations in total plasma homocysteine increase tissue S-adenosylhomocysteine, but responses of S-adenosylmethionine and DNA methylation are tissue specific. J Nutr 132(8):2157-60. [PubMed: 12163655]  [MGI Ref ID J:78135]

Dayal S; Bottiglieri T; Arning E; Maeda N; Malinow MR; Sigmund CD; Heistad DD; Faraci FM; Lentz SR. 2001. Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine beta-synthase-deficient mice. Circ Res 88(11):1203-9. [PubMed: 11397788]  [MGI Ref ID J:115397]

Dayal S; Rodionov RN; Arning E; Bottiglieri T; Kimoto M; Murry DJ; Cooke JP; Faraci FM; Lentz SR. 2008. Tissue-specific downregulation of dimethylarginine dimethylaminohydrolase in hyperhomocysteinemia. Am J Physiol Heart Circ Physiol 295(2):H816-25. [PubMed: 18567702]  [MGI Ref ID J:138223]

Dayal S; Wilson KM; Leo L; Arning E; Bottiglieri T; Lentz SR. 2006. Enhanced susceptibility to arterial thrombosis in a murine model of hyperhomocysteinemia. Blood 108(7):2237-43. [PubMed: 16804115]  [MGI Ref ID J:139462]

Devlin AM; Bottiglieri T; Domann FE; Lentz SR. 2005. Tissue-specific changes in H19 methylation and expression in mice with hyperhomocysteinemia. J Biol Chem 280(27):25506-11. [PubMed: 15899898]  [MGI Ref ID J:100853]

Devlin AM; Singh R; Wade RE; Innis SM; Bottiglieri T; Lentz SR. 2007. Hypermethylation of fads2 and altered hepatic Fatty Acid and phospholipid metabolism in mice with hyperhomocysteinemia. J Biol Chem 282(51):37082-90. [PubMed: 17971455]  [MGI Ref ID J:128932]

Eberhardt RT; Forgione MA; Cap A; Leopold JA; Rudd MA; Trolliet M; Heydrick S; Stark R; Klings ES; Moldovan NI; Yaghoubi M; Goldschmidt-Clermont PJ; Farber HW; Cohen R; Loscalzo J. 2000. Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemia. J Clin Invest 106(4):483-91. [PubMed: 10953023]  [MGI Ref ID J:64041]

Enokido Y; Suzuki E; Iwasawa K; Namekata K; Okazawa H; Kimura H. 2005. Cystathionine beta-synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS. FASEB J 19(13):1854-6. [PubMed: 16160063]  [MGI Ref ID J:102677]

Guzman MA; Navarro MA; Carnicer R; Sarria AJ; Acin S; Arnal C; Muniesa P; Surra JC; Arbones-Mainar JM; Maeda N; Osada J. 2006. Cystathionine beta-synthase is essential for female reproductive function. Hum Mol Genet 15(21):3168-76. [PubMed: 16984962]  [MGI Ref ID J:114850]

Hamelet J; Demuth K; Dairou J; Ledru A; Paul JL; Dupret JM; Delabar JM; Rodrigues-Lima F; Janel N. 2007. Effects of catechin on homocysteine metabolism in hyperhomocysteinemic mice. Biochem Biophys Res Commun 355(1):221-7. [PubMed: 17292331]  [MGI Ref ID J:118638]

Hamelet J; Demuth K; Delabar JM; Janel N. 2006. Inhibition of extracellular signal-regulated kinase in liver of hyperhomocysteinemic mice. Arterioscler Thromb Vasc Biol 26(7):e126-7. [PubMed: 16794227]  [MGI Ref ID J:127993]

Hamelet J; Seltzer V; Petit E; Noll C; Andreau K; Delabar JM; Janel N. 2008. Cystathionine beta synthase deficiency induces catalase-mediated hydrogen peroxide detoxification in mice liver. Biochim Biophys Acta 1782(7-8):482-8. [PubMed: 18541157]  [MGI Ref ID J:137226]

Jiang X; Yang F; Tan H; Liao D; Bryan RM Jr; Randhawa JK; Rumbaut RE; Durante W; Schafer AI; Yang X; Wang H. 2005. Hyperhomocystinemia impairs endothelial function and eNOS activity via PKC activation. Arterioscler Thromb Vasc Biol 25(12):2515-21. [PubMed: 16210565]  [MGI Ref ID J:116854]

Kamath AF; Chauhan AK; Kisucka J; Dole VS; Loscalzo J; Handy DE; Wagner DD. 2006. Elevated levels of homocysteine compromise blood-brain barrier integrity in mice. Blood 107(2):591-3. [PubMed: 16189268]  [MGI Ref ID J:125795]

Kumar M; Tyagi N; Moshal KS; Sen U; Pushpakumar SB; Vacek T; Lominadze D; Tyagi SC. 2008. GABAA receptor agonist mitigates homocysteine-induced cerebrovascular remodeling in knockout mice. Brain Res 1221:147-53. [PubMed: 18547546]  [MGI Ref ID J:139757]

Lentz SR; Erger RA; Dayal S; Maeda N; Malinow MR; Heistad DD; Faraci FM. 2000. Folate dependence of hyperhomocysteinemia and vascular dysfunction in cystathionine beta-synthase-deficient mice. Am J Physiol Heart Circ Physiol 279(3):H970-5. [PubMed: 10993757]  [MGI Ref ID J:64885]

Liao D; Tan H; Hui R; Li Z; Jiang X; Gaubatz J; Yang F; Durante W; Chan L; Schafer AI; Pownall HJ; Yang X; Wang H. 2006. Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance. Circ Res 99(6):598-606. [PubMed: 16931800]  [MGI Ref ID J:125063]

Mikael LG; Genest J Jr; Rozen R. 2006. Elevated homocysteine reduces apolipoprotein A-I expression in hyperhomocysteinemic mice and in males with coronary artery disease. Circ Res 98(4):564-71. [PubMed: 16439690]  [MGI Ref ID J:118991]

Namekata K; Enokido Y; Ishii I; Nagai Y; Harada T; Kimura H. 2004. Abnormal lipid metabolism in cystathionine beta-synthase-deficient mice, an animal model for hyperhomocysteinemia. J Biol Chem 279(51):52961-9. [PubMed: 15466479]  [MGI Ref ID J:128573]

Pacheco-Quinto J; Rodriguez de Turco EB; DeRosa S; Howard A; Cruz-Sanchez F; Sambamurti K; Refolo L; Petanceska S; Pappolla MA. 2006. Hyperhomocysteinemic Alzheimer's mouse model of amyloidosis shows increased brain amyloid beta peptide levels. Neurobiol Dis 22(3):651-6. [PubMed: 16516482]  [MGI Ref ID J:111271]

Powers RW; Gandley RE; Lykins DL; Roberts JM. 2004. Moderate hyperhomocysteinemia decreases endothelial-dependent vasorelaxation in pregnant but not nonpregnant mice. Hypertension 44(3):327-33. [PubMed: 15249551]  [MGI Ref ID J:134575]

Robert K; Chasse JF; Santiard-Baron D; Vayssettes C; Chabli A; Aupetit J; Maeda N; Kamoun P; London J; Janel N. 2003. Altered gene expression in liver from a murine model of hyperhomocysteinemia. J Biol Chem 278(34):31504-11. [PubMed: 12799373]  [MGI Ref ID J:85105]

Robert K; Maurin N; Ledru A; Delabar J; Janel N. 2004. Hyperkeratosis in cystathionine beta synthase-deficient mice: an animal model of hyperhomocysteinemia. Anat Rec A Discov Mol Cell Evol Biol 280(2):1072-6. [PubMed: 15386278]  [MGI Ref ID J:105571]

Robert K; Maurin N; Vayssettes C; Siauve N; Janel N. 2005. Cystathionine beta synthase deficiency affects mouse endochondral ossification. Anat Rec A Discov Mol Cell Evol Biol 282(1):1-7. [PubMed: 15622513]  [MGI Ref ID J:112538]

Robert K; Nehme J; Bourdon E; Pivert G; Friguet B; Delcayre C; Delabar JM; Janel N. 2005. Cystathionine beta synthase deficiency promotes oxidative stress, fibrosis, and steatosis in mice liver. Gastroenterology 128(5):1405-15. [PubMed: 15887121]  [MGI Ref ID J:101303]

Robert K; Pages C; Ledru A; Delabar J; Caboche J; Janel N. 2005. Regulation of extracellular signal-regulated kinase by homocysteine in hippocampus. Neuroscience 133(4):925-35. [PubMed: 15916860]  [MGI Ref ID J:104247]

Robert K; Santiard-Baron D; Chasse JF; Paly E; Aupetit J; Kamoun P; London J; Janel N. 2004. The neuronal SAPK/JNK pathway is altered in a murine model of hyperhomocysteinemia. J Neurochem 89(1):33-43. [PubMed: 15030387]  [MGI Ref ID J:90586]

Schwahn BC; Wendel U; Lussier-Cacan S; Mar MH; Zeisel SH; Leclerc D; Castro C; Garrow TA; Rozen R. 2004. Effects of betaine in a murine model of mild cystathionine-beta-synthase deficiency. Metabolism 53(5):594-9. [PubMed: 15131763]  [MGI Ref ID J:89359]

Sontag E; Nunbhakdi-Craig V; Sontag JM; Diaz-Arrastia R; Ogris E; Dayal S; Lentz SR; Arning E; Bottiglieri T. 2007. Protein phosphatase 2A methyltransferase links homocysteine metabolism with tau and amyloid precursor protein regulation. J Neurosci 27(11):2751-9. [PubMed: 17360897]  [MGI Ref ID J:119470]

Sood HS; Hunt MJ; Tyagi SC. 2003. Peroxisome proliferator ameliorates endothelial dysfunction in a murine model of hyperhomocysteinemia. Am J Physiol Lung Cell Mol Physiol 284(2):L333-41. [PubMed: 12533311]  [MGI Ref ID J:82063]

Tan H; Jiang X; Yang F; Li Z; Liao D; Trial J; Magera MJ; Durante W; Yang X; Wang H. 2006. Hyperhomocysteinemia inhibits post-injury reendothelialization in mice. Cardiovasc Res 69(1):253-62. [PubMed: 16226235]  [MGI Ref ID J:112793]

Vitvitsky V; Dayal S; Stabler S; Zhou Y; Wang H; Lentz SR; Banerjee R. 2004. Perturbations in homocysteine-linked redox homeostasis in a murine model for hyperhomocysteinemia. Am J Physiol Regul Integr Comp Physiol 287(1):R39-46. [PubMed: 15016621]  [MGI Ref ID J:95775]

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Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	100903 B6129PF2/J	(approximate)
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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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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.