B6;129S4-Atm^tm1Bal/J

Stock number: 020943
Product name: ATM-
Research areas: Cancer Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

In this strain a PGK-NEO cassette replaces the exon encoding the ATM kinase domain and the adjacent 3' exon of the Atm gene. Mice homozygous for this targeted mutation succumb to thymic lymphomas by 4 months of age, exhibit neurodegeneration and have applications in studies related to Ataxia-Telangiectasia.

Detailed description

The ATM protein is a DNA double-strand break sensor protein, delaying cell cycle by activating CHK2 checkpoint homolog or arresting cell cycle/initiate apoptosis by phosphorylating p53. These mice carry a targeted mutation of the Atm gene in which the exon encoding the ATM kinase domain and the adjacent 3' exon is disrupted by a PGK-NEO cassette. Mice that are homozygous for the allele are viable, but exhibit retarded growth, and are infertile due to meiotic failure. Homozygotes develop thymic lymphomas that eventually block the thoracic cavity and die before 4 months of age. Mutant mice have fewer pre-B cells and thymocytes, and lower IgG levels. Although ataxia is not observed, homozygotes develop neurodegeneration in the neocortex (large vacuoles in the cerebellar Purkinje cell layer). Heterozygotes are viable and fertile.

Development

A targeting vector designed by Drs. Yang Xu and David Baltimore (Massachusetts Institute of Technology) containing a PGK-NEO cassette was inserted into position 5979, disrupting the exon encoding the ATM kinase domain and the adjacent 3' exon. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric mice were bred to C57BL/6 mice. The mice were maintained on a mixed B6;129S4 background. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Atm^tm1Bal
Name: targeted mutation 1, David Baltimore
MGI accession ID: MGI:1926343
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Atm
Marker name: ataxia telangiectasia mutated
Chromosome: 9
Strain of origin: 129S4/SvJae
Molecular note: Part of an exon encoding the kinase-conserved sequence of Atm and the following 3' exon was replaced with a PGK-neomycin cassette.