C57BL/6-Mia2^cpto/J

Stock number: 017461
Research areas: Cardiovascular Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

These Mia2^cpto ENU-induced mutant mice possess a missense mutation in exon 3 of the melanoma inhibitory activity 2 (Mia2) gene. These mutant mice may be useful in studying the regulation and secretion of circulating cholesterol and triglycerides.

Detailed description

These Mia2^cpto ENU-induced mutant mice possess a missense mutation in exon 3 of the melanoma inhibitory activity 2 (Mia2) gene. Homozygotes are viable and fertile. Mia2 encodes many transcripts due to alternative splice and promoter use. Transcripts including exon 3, which contains the cpto mutation, are specifically expressed in liver and small intestine. Localized to endoplasmic reticulum exit sites, MIA2 plays a role in the regulation of sorting in the secretory pathway. Variations in Mia2 transcript levels have been implicated in several types of liver disease. These MIA2 mutants exhibit lower circulating very-low-density lipoprotein VLDL, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides. They have no changes in glucose levels, insulin levels, body weight, fat mass or lean mass as compared to controls. These mutant mice may be useful in studying the regulation and secretion of circulating cholesterol and triglycerides.

Development

Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder C57BL/6J mice, a forward genetic screen was utilized to identify mice exhibiting a recessive mutation causing changes in plasma cholesterol. A mutation was mapped by SNP genotyping and a critical interval was defined. Candidate genes within this interval were sequenced to find the in the melanoma inhibitory activity 2 (Mia2) gene. Sequencing of this gene identified a T to C transition in exon 3 of Mia2 resulting in a phenylalanine to serine missense mutation (F91S). These Mia2^cpto mice were bred to C57BL/6J mice to establish a colony. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation.

Allele

Symbol: Mia2^cpto
Name: couch potato
MGI accession ID: MGI:5290109
Generation method: Chemically induced (ENU)
Synonyms: Mia2^F91S
Marker symbol: Mia2
Marker name: melanoma inhibitory activity 2
Chromosome: 12
Strain of origin: C57BL/6J
Molecular note: ENU mutagenesis induced a T to C mutation that results in the amino acid substitution of serine for phenylalanine at position 91 (F91S).