B6.Cg-Tg(SOD1*G93A)^dl1Gur/J

Stock number: 002299
Product name: G93A SOD1
Research areas: Metabolism Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

These C57BL/6J-congenic SOD1-G93A transgenic mice carry a reduced copy number of the variant human superoxide dismutase 1 soluble gene transgene, Tg(SOD1*G93A)^dl1Gur. These mice exhibit a delayed onset of phenotype when compared to the original high copy number C57BL/6J-congenic SOD1-G93A transgenic mice (B6.Cg-Tg(SOD1*G93A)1Gur/J; Stock No. 004435). These mice are useful for studies of neuromuscular disorders, including Amyotrophic Lateral Sclerosis (ALS).

Detailed description

Mice carrying the transgene exhibit paralysis resulting in a reduced life expectancy. They serve as a model for human amyotrophic lateral sclerosis (ALS). The transgene carries a variant of the human Superoxide dismutase-1 gene (glycine to alanine at position 93). Paralysis is due to loss of motor neurons from the spinal cord. The onset of the ALS phenotype is delayed compared to the original high copy number C57BL/6J-congenic SOD1-G93A transgenic mice (B6.Cg-Tg(SOD1*G93A)1Gur/J; Stock No. 004435) because of a reduction in transgenic copy number (see details below). This reduction most likely occurred during the importation and establishment of the original high copy number mutant transgenic strain. Mice on the B6SJL background (Stock No. 002300) become paralyzed in one or more limbs beginning around six to seven months of age. Life expectancy is normally four to six weeks beyond onset of symptoms. The transgene was backcrossed to C57BL/6J for five generations. The ALS phenotype on this genetic background has not been characterized; however, the onset of the ALS phenotype does not appear to be accelerated (March 1996). One advantage to working with this strain would be its inbred background.

In 2014, Genetic Quality Assurance/Control program at The Jackson Laboratory Repository assessed the survival of a cohort of hemizygous mice (16 females and 9 males; mixed siblings and non-siblings). This showed all tested animals survived beyond 200 days, ~50% survival at 275-300 days of age, and all tested animals die before one year of age. This confirms that reduced transgene copy number in these C57BL/6J-congenic SOD1-G93A transgenic mice (Stock No. 002299) results in a slower progressing model of ALS compared to the original high copy number C57BL/6J-congenic SOD1-G93A transgenic mice (Stock No. 004435; reported to have ~50% survival at 157 days of age).

Development

This transgenic strain was made in the laboratory of Dr. Mark E. Gurney at Northwestern University. The transgene contains the mutant human SOD1 containing the Gly⁹³ -->Ala (G93A) substitution and was microinjected into (C57BL/6 X SJL)F1 fertilized eggs. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) for at least five generations.

Allele

Symbol: Tg(SOD1*G93A)^dl1Gur
Name: transgene insertion dl 1, Mark E Gurney
MGI accession ID: MGI:2671112
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: G1L; G93A SOD1; mSOD1-Tg; Tg(SOD1-G93A)^dl1Gur; TgN(SOD1-G93A)1Gur^dl; TgN(SOD1-G93A)1Gurdl; TgN[SOD1-G93A]^dl1Gur; TgNSOD1-G93A
Marker symbol: Tg(SOD1*G93A)^dl1Gur
Marker name: transgene insertion dl 1, Mark E Gurney
Marker synonyms: G1L; G93A SOD1; mSOD1-Tg; Tg(SOD1-G93A)^dl1Gur; TgN(SOD1-G93A)1Gur^dl; TgN(SOD1-G93A)1Gurdl; TgN[SOD1-G93A]^dl1Gur; TgNSOD1-G93A
Chromosome: 12
Strain of origin: (C57BL/6 x SJL)F1
Expressed genes: SOD1,superoxide dismutase 1,human
Molecular note: This subline has approximately 30% fewer copies of the transgene construct than the high copy number line, Tg(SOD1*G93A)1Gur. The reduction most likely occurred during the importation and establishment of the high copy number mutant transgenic line. The transgene is composed of a variant of the human superoxide dismutase 1 gene (SOD1) carrying a glycine to alanine substitution at position 93 (G93A). The G93A mutation does not alter the activity of the protein.
General note: Transgenic mice on a C57BL/6 congenic background exhibit paralysis resulting in a reduced life expectancy, and may serve as a model for human amyotrophic lateral sclerosis (ALS). Paralysis in these mice is due to loss of motor neurons from the spinal cord. The onset of the ALS phenotype in these mice is delayed compared to mice carrying the original high copy number transgene Tg(SOD1*G93A)1Gur.

Transgenic mice on a genetic background involving C57BL/6 and SJL become paralyzed in one or more limbs beginning around six to seven months of age. Life expectancy for these mice is normally four to six weeks beyond onset of symptoms.