B6.Cg-Tg(SOD1*G85R)148Dwc/J

Stock number: 008248
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

These G85R-SOD1 transgenic mice may be useful in studying neuromuscular disorders, including Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease).

Detailed description

Mice hemizygous for this G85R-SOD1 transgene are viable and fertile, with transgenic expression of a G85R mutant form of human SOD1 associated with human familial Amyotrophic Lateral Sclerosis (ALS). Mice from this founder line (line 148) exhibit unaltered endogenous SOD1 activity; the G85R mutation is characterized as an "enzymatically inactive" mutation. Like wildtype SOD1, the G85R mutant SOD1 protein also forms monomer-misfolded oligomers associated with degenerating motor neurons.

Hemizygotes develop symptoms and pathology resembling human ALS; becoming paralyzed in one or more limbs due to loss of motor neurons from the spinal cord. On the C57BL/6 genetic background, hemizygous mice have a longer lifespan (median lifespan of 361 days). After the first initial phenotype observation, the disease progresses rapidly with death around 12-13 months of age. The onset and progression of motor dysfunction is accompanied by weight loss. For more detailed information, please view graph of B6.Cg-Tg(SOD1*G85R)148Dwc/J survival and weight data 2009-2010. [pdf]

These G85R-SOD1 transgenic mice may be useful in studying neuromuscular disorders, including Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. As the G85R-SOD1 transgenic mice were originally created on a mixed genetic background, it should be noted that the phenotype of these transgenic mice on a C57BL/6-congenic background may vary greatly from that originally described. We will modify the strain description if necessary as published results become available.

Development

The G85R-SOD1 (or SOD1-G85R) transgene was designed with a mutant human SOD1 gene (harboring a single amino acid substitution of glycine to arginine at codon 85) driven by its endogenous human promoter. This 12 kb transgene was microinjected into hybrid (C57BL/6J x C3H/HeJ)F2 mouse embryos and transgenic G85R-SOD1 mice (founder line 148) were established. These mice were then backcrossed to C57BL/6J inbred mice for many generations prior to arrival at The Jackson Laboratory.

Allele

Symbol: Tg(SOD1*G85R)148Dwc
Name: transgene insertion 148, Don W Cleveland
MGI accession ID: MGI:2182171
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(SOD1*G85R)148Dwc
Marker name: transgene insertion 148, Don W Cleveland
Chromosome: UN
Strain of origin: Not Applicable
Expressed genes: SOD1,superoxide dismutase 1,human
Molecular note: A 12 kb genomic fragment of human SOD1 carrying a glycine to arginine substitution at amino acid 85 (G85R), a mutation associated with familial amyotrophic lateral sclerosis (ALS), was used as the transgene.
General note: Transgenic animals initially exhibit hindlimb weakness that spreads with rapid progression to forelimbs and results in muscle atrophy and complete paralysis within 2 weeks. Founders 148-G85R and 74-G85R are the highest and lowest expressing transgenic lines, respectively, and differ in onset of clinical symptoms, presumably due to gene dosage. Founder 148-G85R exhibits muscle weakness at 8-10 months of age whereas founder 74-G85R exhibits the phenotype 12-14 months of age. Despite the difference in disease onset both founders show the same rate of disease progression after appearance of initial symptoms.