C57BL/6J-Otc^spf-J/J

Stock number: 001672
Product name: sparse fur Jackson
Research areas: Dermatology Research, Metabolism Research, Mouse/Human Gene Homologs

Description

These mice carry a spontaneous mutation at the Otc locus characterized by coat and skin abnormalities. With higher residual enzyme activity these mice have normal plasma ammonia and plasma orotic acid at baseline and mild amino acid perturbations.

Detailed description

The transversion in exon 3 of ornithine transcarbamylase in Otc^spf-J mice leads to normal levels of mRNA with low levels of mature protein. With higher residual enzyme activity, Otc^spf-J mice were found to have normal plasma ammonia and orotate. Baseline plasma amino acid profiles were consistent with mild OTCD: elevated glutamine, and lower citrulline and arginine. In contrast to wild type, Otc^spf-J mice displayed baseline elevations in cerebral amino acids with depletion following immune challenge with polyinosinic:polycytidylic acid. These mice may be suitable for mechanistic studies of mild OTCD and the exploration of cerebral pathophysiology during acute decompensation that characterizes proximal urea cycle dysfunction in humans.

Allele

Symbol: Otc^spf-J
Name: sparse fur Jackson
MGI accession ID: MGI:1856372
Generation method: Spontaneous
Attributes: Hypomorph
Marker symbol: Otc
Marker name: ornithine transcarbamylase
Chromosome: X
Strain of origin: C57BL/6J
Molecular note: This allele was identified from the results of a noncomplementation test with Otc^spf. A missense mutation was identified, with a c.240A>T transversion in exon 3, leading to a lysine to asparagine substitution (p.K80N). The K80 residue is located outside the carbamoyl phosphate and ornithine binding regions. qRT-PCR confirmed similar levels of hepatic mRNA in heterozygous females and hemizygous males as in wild-type mice, while Western blot showed drastically reduced hepatic protein levels. Otc enzyme activity is 10-12% of wild-type levels.