B6.129P2-Cbs^tm1Unc/J

Stock number: 002853
Product name: CBS-
Research areas: Internal/Organ Research, Metabolism Research, Mouse/Human Gene Homologs

Description

These Cbs knock-out mice exhibit severe growth retardation and elevated plasma homocysteine levels.

Detailed description

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.

Development

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-Cbs^tm1Unc strain was generated by crossing the Cbs^tm1Unc mutation onto C57BL/6J mice.

Allele

Symbol: Cbs^tm1Unc
Name: targeted mutation 1, University of North Carolina
MGI accession ID: MGI:1857139
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: CBS; CBS-; Cbs^-
Marker symbol: Cbs
Marker name: cystathionine beta-synthase
Marker synonyms: CBSL; HIP4; MGC:18856; MGC:18895; MGC:37300
Chromosome: 17
Strain of origin: 129P2/OlaHsd
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.
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).