C57BL/6J-Trpm1^tvrm27/PjnJ

Stock number: 030569
Product name: Tvrm27 A1068T
Research areas: Developmental Biology Research, Research Tools, Sensorineural Research

Description

This ENU-generated tvrm27 mutation of Trpm1 creates a substitution mutant allele of a single base pair change, c.G3399A, in exon 2 resulting in a substitution of alanine to threonine (p.A1068T). Heterozygotes exhibit a reduced b-wave ERG amplitude, and the b-wave is absent in homozygotes. These mice may be suitable for use in studies related to complete congenital stationary night blindness.

Detailed description

The targeted Trpm1 gene encodes a calcium permeable cation channel also known as melastatin. Mutations in this gene have been associated with autosomal recessive night blindness, congenital stationary (complete), 1C. This ENU-generated dominant negative tvrm27 mutation of Trpm1 creates a substitution mutant allele of a single base pair change, c.G3399A, in exon 2 resulting in a substitution of alanine to threonine (p.A1068T) in the predicted channel pore region. Expression of Trpm1 is detected by immunohistochemistry in the dendritic tips of depolarizing bipolar cells in the retina. In dark-adapted conditions, ERG b-wave amplitude is reduced by 32% in heterozygotes, and is absent in homozygotes, while the a-wave is unaltered (no b-wave ERG phenotype). Homozygotes are viable and fertile.

Development

Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in C57BL/6J male mice, a forward genetic screen was utilized to identify G3 mice exhibiting a recessive mutation causing abnormal electroretinograms (ERGs). Sequencing of candidate gene Trpm1 revealed a single base pair change, c.G3399A in exon 2, resulting in a substitution of alanine to threonine (p.A1068T). Upon transfer, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Trpm1^tvrm27
Name: translational vision research model 27
MGI accession ID: MGI:4867880
Generation method: Chemically induced (ENU)
Attributes: Dominant negative
Marker symbol: Trpm1
Marker name: transient receptor potential cation channel, subfamily M, member 1
Marker synonyms: 4732499L03Rik; CSNB1C; LTRPC1; melastatin; Mlsn1
Chromosome: 7
Strain of origin: C57BL/6J
Molecular note: ENU mutagenesis induced a G to A point mutation that results in the amino acid substitution of threonine for alanine at position 1068 (A1068T). Immunohistochemistry confirmed normal expression and localization of the protein product. However, channel function is lost.