FVB(Cg)-Tg(Thy1-SOD1*G93A)T3Hgrd/J

Stock number: 008230
Strain synonyms: FVB-Thy1.2-G93A, FVB-T3
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

Thy1.2-G93A (or T3) transgenic mice express human G93A mutant SOD1 (G93A-SOD1)in neurons throughout the brain and spinal cord (including spinal motor neurons), and may be useful in studying neuromuscular disorders, such as Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease).

Detailed description

These Thy1.2-G93A transgenic mice have a human SOD1 cDNA harboring the G93A mutation driven by the murine Thy1.2 expression cassette. Expression of the G93A mutant SOD1 (G93A-SOD1) is directed to neurons throughout the brain and spinal cord (including spinal motor neurons). In addition, mutant SOD1 immunoreactivity is selectively distributed in axons and nerve endings at the neuromuscular junctions. While Thy1.2-G93A hemizygous mice from founder line T3 are viable and fertile with no clinical or pathological signs of motor abnormalities up to two years of age, neuronal expression of mutant SOD1 in homozygous Thy1.2-G93A mice from founder line T3 (also called T3T3 mice) develop an Amyotrophic Lateral Sclerosis (ALS)-like motor neuron disease between one to two years of age, characterized by motor neuron degeneration, muscle denervation, paralysis, and muscle weakness with cytosolic dendritic ubiquitinated SOD1 aggregates as the dominant pathological feature. Additionally, when these T3 mice are bred with N29 hSOD1 mice (see Tg(SOD1)2Gur mice; Stock No. 002297 and 002298), T3/hSOD1 double hemizygous offspring develop an ALS-like motor neuron disease between one to two years of age. These Thy1.2-G93A (or T3) 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. It should be noted that the phenotype of these mice could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A transgene was designed with a modified regulatory region of the "murine Thy1.2 gene" (extending from the promoter to the intron following exon 4, excluding exon 3 and its flanking introns) upstream of a mutant human superoxide dismutase cDNA sequence (G93A-SOD1; harboring a single amino acid substitution of glycine to alanine at codon 93). This transgene was microinjected into FVB fertilized oocytes and Thy1.2-G93A transgenic founder males (line T3) were bred to FVB/NHsd females. Transgenic males were backcrossed to FVB/NHsd females for 5 generations, then bred with a Thy1.2-G93A line T3 female (on a mixed FVB, C57BL/6, CBA genetic background) for one generation, and then backcrossed to FVB/NHsd females for an additional seven or more generations prior to arrival at The Jackson Laboratory in 2008. Upon arrival, transgenic mice were bred with FVB/NJ to establish the colony. The pedigree information provided by the donating investigator suggests the Y chromosome is expected to be FVB/N background.

Allele

Symbol: Tg(Thy1-SOD1*G93A)T3Hgrd
Name: transgene insertion T3, Casper Hoogenraad
MGI accession ID: MGI:3785090
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Thy1-SOD1*G93A)T3Hgrd
Marker name: transgene insertion T3, Casper Hoogenraad
Chromosome: UN
Strain of origin: FVB
Expressed genes: SOD1,superoxide dismutase 1,human
Molecular note: The transgene construct contains a modified regulatory region of the murine thy1.2 gene (extending from the promoter to the intron following exon 4, excluding exon 3 and its flanking introns), upstream of a mutant human superoxide dismutase cDNA sequence (G93A-SOD1) harboring a single amino acid substitution of glycine to alanine at codon 93. Transgene expression throughout the brain and spinal cord was determined by western blot. Line T3 was characterized further.