B6.129X1-Sarm1^tm1Aidi/J

Stock number: 018069
Product name: MyD88-5^-
Research areas: Neurobiology Research, Research Tools

Description

In this knock-out strain exons 3-6 of the Sarm1 gene are disrupted. These mice exhibit enhanced resistance to oxygen and glucose deprivation induced neuronal death and have applications in studies of neurodegeneration.

Detailed description

Sarm1, sterile alpha and HEAT/Armadillo motif containing 1, also known as MyD88-5, is highly conserved across phyla, expressed predominantly in neurons, is a member of the TIR domain-containing family of adaptor molecules for Toll-like receptors, and promotes neurodegeneration. Mice that are homozygous for this targeted mutation of Sarm1 are viable and fertile. No gene product (protein) is detected by Western blot analysis of brain from homozygotes. Homozygotes are less sensitive to oxygen and glucose deprivation induced cell death in a model for neuronal viability in hippocampal slices. TLR-mediated signaling pathways in homozygotes are not altered. During backcrossing, the Y chromosome has been fixed to the C57BL/6 genetic background.

Development

A targeting vector containing NEO cassette (in reverse orientation) was used to disrupt exons 3 through 6 of the gene. The construct was electroporated into unspecified 129X1/SvJ (129/SvJ)-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and the donating investigator reported that they were backcrossed to C57BL/6 for 15 generations (see SNP note below). Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Allele

Symbol: Sarm1^tm1Aidi
Name: targeted mutation 1, Aihao Ding
MGI accession ID: MGI:3765956
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Sarm1
Marker name: sterile alpha and HEAT/Armadillo motif containing 1
Chromosome: 11
Strain of origin: 129X1/SvJ
Molecular note: Exons 3 through 6 were replaced with a neo cassette in reverse orientation. The absence of protein product was confirmed by western blot analysis on protein extracted from the brain.