B6.Cg-Tg(SOD1*G37R)42Dpr/J

Stock number: 008342
Product name: G37R(42) SOD1
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

These transgenic mice express elevated levels of SOD1 and develop pathology resembling human Amyotrophic Lateral Sclerosis (ALS). These mice may be useful in studying neuromuscular disorders, including ALS.

Detailed description

Mice hemizygous for this G37R-SOD1 transgene are viable and fertile. The expressed G37R mutant form of human SOD1 is characterized as an enzymatically active, "gain of adverse function" mutation. Hemizygotes develop symptoms and pathology resembling human Amyotrophic Lateral Sclerosis (ALS), with paralyzation in one or more limbs attributable to the loss of motor neurons from the spinal cord. Transgenic mice from the highest expressing founder line (G37R(42) or line 42) express a 14-fold increase in SOD1 activity in spinal cord High expression of G37R-SOD1 is associated with ALS pathology in motor neurons of the spinal cord and brainstem, widespread degenerative changes in other neuronal populations, and mild-to-moderate vacuolar changes in kidney. These high-expressing G37R(42) (or G37R-SOD1 line 42) transgenic mice may be useful in studying neuromuscular disorders, including Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease).

The original publication by Wong et al assessed survival on a mixed genetic background and noted death occurring around 3.5-4 months of age. Since then, this allele has been backcrossed to C57BL/6J and made fully congenic. This change in genetic background has resulted in a change in disease onset and progression. In a study conducted at The Jackson Laboratory involving a cohort of 21 female transgenic mice, it was found that 90% of the animals survived to 25 weeks, 50% survived to 27 weeks, and death occurred in 100% of the mice by 29 weeks. IN SUMMARY: ON A C57BL/6J BACKGROUND SURVIVAL IS INCREASED TO 6-7 MONTHS.

Development

The G37R-SOD1 (or SOD1-G37R) transgene was designed with a mutant human SOD1 gene (harboring a single amino acid substitution of glycine to arginine at codon 37) driven by its endogenous human promoter. This 12 kb transgene was microinjected into hybrid (C57BL/6J x C3H/HeJ)F2 mouse embryos and transgenic G37R-SOD1 mice (founder line 42) 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*G37R)42Dpr
Name: transgene insertion 42, Donald L Price
MGI accession ID: MGI:3574014
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(SOD1*G37R)42Dpr
Marker name: transgene insertion 42, Donald L Price
Chromosome: UN
Strain of origin: (C57BL/6J x C3H/HeJ)F2
Expressed genes: SOD1,superoxide dismutase 1,human
Molecular note: A 12 kb genomic DNA fragment containing a mutated form of human SOD1 with a glycine to arginine substitution at amino acid 37 (G37R) was used for the transgene. The G37R mutation is found in some cases of familial amyotrophic lateral sclerosis (FALS).