B6(C3H)-Sod1^m1H/J

Stock number: 020440
Research areas: Developmental Biology Research, Neurobiology Research

Description

Sod1^D83G ENU-induced mutant mice possess a missense mutation in exon 3 of the Sod1 gene. These mutant mice may be useful in studying the effects of SOD1 protein regulation on the development of amyotrophic lateral sclerosis and motor neuron disease. They are a useful tool for separating the effects of central neuronal death from the peripheral distal neuropathy.

Detailed description

These Sod1^D83G ENU-induced mutant mice possess a missense mutation in exon 3 of the superoxide dismutase 1 (Sod1) gene. SOD1 is a widely expressed isozyme responsible for destroying free superoxide radicals. SOD1 mutations, including SOD1*D83G, are known to cause Lou Gehrig's disease (Amyotrophic lateral sclerosis; ALS)/motor neuron disease (MND). These mutant mice produce the same mRNA levels as wildtype mice but contain decreased amounts of mutant SOD1 protein, leading to a dose dependant decrease in dismuatase activity. Homozygotes mice are not produced in a Mendelian ratio. They develop a degeneration of the lower and upper motor neurons between 6 and 15 weeks of age. This neuronal cell death ceases in adulthood and the mice do not become paralyzed. However, motor ability continues to deteriorate after 15 weeks of age in homozygous mutants. . This motor dysfunction is underlined by a progressive distal denervation of the neuromuscular junctions of the extensor digitorum longus hindlimb muscle between 15 and 52 weeks of age, leading to progressive peripheral neuropathy. These mice have a reduced life span, and they develop liver tumors, tremors, reduced pelvic elevation, significant sensory deficits. Heterozygotes are viable and fertile, and have a phenotype similar to wildtype littermates, except for in cage motor ability.

Development

Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder male C57BL/6J mice, a reverse genetic screen was utilized to identify mice with a mutation in the superoxide dismutase 1 (Sod1) gene. Males were bred with C3H/HeH females and sperm from F1 males was screened for mutations in Sod1. A mutation was mapped with Sanger sequencing and an A to G transition in exon 3 of Sod1 resulting in an aspartic acid to glycine missense mutation (D83G). Sperm from Sod1^D83G F1 males was used for in vitro fertilization of C57BL/6J oocytes. These Sod1^D83G mice were bred to C57BL/6J mice for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation.

Allele

Symbol: Sod1^m1H
Name: mutation 1, Harwell
MGI accession ID: MGI:5575771
Generation method: Chemically induced (ENU)
Marker symbol: Sod1
Marker name: superoxide dismutase 1, soluble
Chromosome: 16
Strain of origin: C57BL/6J
Molecular note: ENU mutagenesis induced an A to G transition in exon 3 that results in an aspartic acid to glycine missense mutation (D83G). Dismutase activity of the mutant protein is severely reduced compared to the wild-type protein.