B6.Cg-Tg(SOD1*G93A)1Gur/J

Stock number: 004435
Product name: SOD1-G93A
Strain synonyms: B6.SOD1-G93A
Research areas: Metabolism Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

SOD1-G93A transgenic mice express a G93A mutant form of human SOD1 and may be useful in studying neuromuscular disorders such as Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease).

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This SOD1-G93A transgene is available on C57BL/6J (Stock No. 004435), B6SJL (Stock No. 002726) and FVB/NJ (Stock No. 013199). In addition, a very low expressing variant on B6SJL is available (Stock No. 032166).

Detailed description

Mice hemizygous for this SOD1-G93A (also called G93A-SOD1) transgene are viable and fertile, with transgenic expression of a G93A mutant form of human SOD1. This founder line (often referred to as G1H) is reported to have high transgene copy number. Hemizygotes exhibit a phenotype similar to amyotrophic lateral sclerosis (ALS) in humans; becoming paralyzed in one or more limbs with paralysis due to loss of motor neurons from the spinal cord. Motor neuron degeneration has been associated with function and/or degeneration of astrocytes, the major glial cell type of the nervous system. Transgenic mice have an abbreviated life span: 50% survive at 157.1+/-9.3 days (in contrast to the mixed B6SJL background where 50% survival is observed at 128.9+/-9.1 days). Female hemizygotes are poor breeders, and rarely produce more than one litter before the onset of disease. In contrast to LPS-induced microglia and activated M1/M2 macrophages, spinal cord microglia activated by disease progression do not upregulate genes that display a bias to either an M1 (neurotoxic) phenotype or an M2 (protective) phenotype. The pattern of gene expression in SOD1^G93A activated microglia represents a unique ALS-specific signature. These SOD1-G93A (also called G93A-SOD1) transgenic mice may be useful in studying neuromuscular disorders, including Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease).

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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 SOD1-G93A transgenic mice were originally created on a mixed genetic background, it should be noted that the phenotype of the congenic mice (Stock No. 004435) could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

The SOD1-G93A (or G93A-SOD1) transgene was designed with a mutant human SOD1 gene (harboring a single amino acid substitution of glycine to alanine at codon 93) driven by its endogenous human SOD1 promoter. This transgene was injected into fertilized B6SJLF1 mouse eggs and founder animals were obtained. Transgenic mice on a mixed B6SJL genetic background were sent to The Jackson Laboratory (as Stock No. 002726). Upon arrival, some mice were backcrossed to C57BL/6J for at least 10 generations to generate this congenic strain (Stock No. 004435). The backcross was completed in July 2002.



Note that the nomenclature refers to the G93A amino acid (aa) change in the 153 aa SOD1 protein (Tu et al. 1996 PNAS 93:3155 [PMID:8610185]), whereas the Ensembl transcript numbering consensus is an 154 aa SOD1 protein - thus predicting this mutation to be G94A. It is likely that the source of the numbering discrepancy is that the protein has cleaved off the N-terminal methionine (see Barra et al. 1980 FEBS Lett 120:53 [PMID:7002610]), whereas the genomic sequence database assumes the N-terminal methionine is still present.

Allele

Symbol: Tg(SOD1*G93A)1Gur
Name: transgene insertion 1, Mark E Gurney
MGI accession ID: MGI:2183719
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(SOD1*G93A)1Gur
Marker name: transgene insertion 1, Mark E Gurney
Chromosome: 12
Strain of origin: (C57BL/6 x SJL)F1
Expressed genes: SOD1,superoxide dismutase 1,human
Molecular note: This transgenic subline (designated G1H in J:76718) is derived from the G1 parental transgenic line (originally described in J:32665). This line carries a 40% expansion in transgene copy number compared to the original G1 line (described in J:32665, in MGI as Tg(SOD1*G93A)2Gur). The transgene construct is composed of the human SOD1 gene carrying a glycine to alanine transition at position 93 (G93A). The G93A mutation does not alter the activity of the protein. This line carries a high copy number maps to Mus Chr12:97,165,800 (coordinates from MGSC ver 37, mm9).
General note: This line, G1H, was derived from the original G1 line (now designated Tg(SOD1*G93A)2Gur) reported in J:32665.

Transgenic mice on a background that involves C57BL/6 and SJL express high levels of the transgene with a 4-fold increase in SOD activity, and exhibit a phenotype similar to amyotrophic lateral sclerosis (ALS) in humans. Hemizygous transgenic mice become paralyzed in one or more limbs and have a life span of approximately 19-23 weeks. Paralysis is due to loss of motor neurons from the spinal cord.