B6.129P2-Scp2^tm1Usee/J

Stock number: 006620
Product name: Scp2-
Research areas: Internal/Organ Research, Metabolism Research

Description

Mice homozygous for this knock-out mutation demonstrate defective catabolism of fatty acids and have a pronounced accumulation of phytanic acid.

Detailed description

Mice homozygous for this targeted mutation are viable and fertile and do not display any gross physical or behavioral abnormalities. No protein product from the targeted gene is detected in liver tissue. Northern blot experiments show a low-intensity signal from a non-functional truncated transcript, however. Histologically, greater numbers of peroxisomes are observed in the livers of these mice. Liver function appears normal based on liver enzyme levels, but cholesterol and triglyceride storage pools are depleted. Hepatic gene expression is altered. Higher expression levels of liver fatty acid binding protein and multiple peroxisomal beta-oxidation enzymes are observed. Whereas plasma insulin and cholesterol concentrations are normal, triglycerides are slightly higher and free fatty acid and glucose concentrations are moderately lower in homozygous mice. Food intake is significantly higher in homozygotes as compared to control animals. A pronounced accumulation of phytanic acid is observed in homozygotes. Diets supplemented with 5 mg/g phytol (a metabolic precursor of branched-chain fatty acids) cause weight loss, decreased lipid and glucose levels in serum, liver disease, ataxia, peripheral neuropathy, and sudden cardiac death in the mice. These mice demonstrate defective catabolism of branched-chain fatty acids and altered bile acid synthesis due to impaired peroxisomal beta-oxidation.

Development

A targeting vector containing a neomycin resistance gene was used to replace exon 14 of the gene. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric animals were crossed with C57BL/6 for at least ten generations before the line was made homozygous for the mutation.

Allele

Symbol: Scp2^tm1Usee
Name: targeted mutation 1, Udo Seedorf
MGI accession ID: MGI:1857809
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Scp2
Marker name: sterol carrier protein 2, liver
Chromosome: 4
Strain of origin: 129P2/OlaHsd
Molecular note: Exon 14 was disrupted by the insertion of a neomycin cassette. Sequence analysis of truncated transcript identified by Northern analysis, showed that an aberrant splice pattern resulted in the excision of exon 14. The joining of exons 13 and 15 resulted in a frameshift mutation which introduced a stop codon in exon 15, upstream of an essential peroxisomal targeting signal. Western analysis revealed an absence of normal protein in the livers of homozygous mutant mice.