The phenotype of cystathionine-beta synthase deficient mice on the C57BL/6J background has not been characterized. Homozygous mice on the mixed B6,129 background 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.
The Cbs-deficient mutation 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. This C57BL/6J-Cbstm1Unc strain was generated by crossing the Cbstm1Unc mutation onto C57BL/6J mice.
|Allele Name||targeted mutation 1, University of North Carolina|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CBS; CBS-; Cbs-|
|Gene Symbol and Name||Cbs, cystathionine beta-synthase|
|Strain of Origin||129P2/OlaHsd|
|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 mice demonstrated that no stable transcript is produced from this allele.|
|Mutations Made By|| |
Dr. Nobuyo Maeda, University of North Carolina at Chapel Hill
When maintaining a live colony, heterozygotes may be bred to wildtype siblings. The expected coat color from breeding is black.
When using the CBS- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002853 in your Materials and Methods section.