B6.129S7-Sod2^tm1Leb/J

Stock number: 002973
Product name: SOD2^m1BCM
Research areas: Metabolism Research, Neurobiology Research

Description

Mice homozygous for this targeted mutation of mouse Sod2 (superoxide dismutase 2, mitochondrial) are embryonic lethal. Crosses with DBA/2J inbred mice enhance homozygous viability and produce animals exhibiting severe wasting and progressive ataxia.

Detailed description

Original studies of this strain, first published in 1996, describe homozygous animals that died within 21 days of birth and exhibited several novel pathogenic phenotypes including severe anemia, degeneration of neurons in the basal ganglia and brainstem, progressive motor disturbances, and myocardial injury. Applications included studies of idiopathic cardiomyopathy and sporadic motor neuron disease.

It has been found, however, that mice homozygous for the Sod2^tm1Leb mutation on the current C57BL/6 genetic background (backcross generation N5+25 - July, 2017) are embryonic lethal. In one recent study, heterozygote x heterozygote crosses produced no homozygous mutants at P0-P1 (0/40 pups; unpublished).

Improved homozygous viability has been demonstrated in matings of B6.129S7-Sod2^tm1Leb/J (Stock# 002973) mutant mice with DBA/2J inbred animals (Stock# 000671). Intercrosses of F1 animals yield F2 homozygous pups at a lower-than-predicted Mendelian percentage, but they have a median survival time of 12 days. The C57BL/6-DBA/2J (B6D2F2) mixed background mutant animals (not currently offered by The Jackson Laboratory) display severe wasting and progressive ataxia. The heart and brain have not been examined histologically. This data has not been published (July, 2017).

Development

The Sod2^tm1Leb targeted mutation was made by Dr. Russell Lebovitz. A 1.5 Kb HindIII fragment containing exons 1 and 2 of the Sod2 gene, as well as approximately 500bp immediately 5' of exon 1, was replaced with a human hypoxanthine phosphoribosyltransferase minigene driven by the phosphoglycerate kinase promoter. The transcription and translation start sites, the mitochondrial targeting sequence, and one of the three histidines that bind directly to the manganese cofactor, have been eliminated. The 129S7/SvEvBrd-Hprt^b-m2-derived AB 2.1 ES cell line was used. The Sod2^tm1Leb targeted mutation was initially backcrossed more than 5 times to C57BL/6 mice prior to arrival at The Jackson Laboratory. A further 25 generations of backcrossing to C57BL/6J have subsequently occurred (July, 2017).

Allele

Symbol: Sod2^tm1Leb
Name: targeted mutation 1, Russell M Lebovitz
MGI accession ID: MGI:1857480
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Sod2
Marker name: superoxide dismutase 2, mitochondrial
Chromosome: 17
Strain of origin: 129S7/SvEvBrd-Hprt^b-m2
Molecular note: A human HPRT minigene driven by the PGK promoter replaced exons 1 and 2, and sequences approximately 500 bp immediately 5' of exon 1. The replaced region encodes the transcription and translation start sites, the mitochondrial targeting sequence, and one of three histidines that bind directly to the manganese cofactor. Northern blot analysis of brain did not detect mRNA in homozygous mutant mice. Enzyme activity assays of heart did not detect active protein in homozygous mutant mice.