Amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease)
See a complete list of JAX® Mice for amyotrophic lateral sclerosis research.
Amyotrophic lateral sclerosis (ALS) usually attacks both upper and lower motor neurons and causes degeneration throughout the brain and spinal cord. Early symptoms in 50% percent of affected people are a painless weakness in a hand, foot, arm, or leg. Other early symptoms include speech-swallowing and difficulty walking. ALS most commonly strikes people between 40 and 70 years old, affecting as many as 30,000 Americans at any given time. Like other neuromuscular diseases, ALS is complex, but spontaneous mouse mutants are helping scientists identify the responsible genes and biochemical pathways (The ALS Association).
JAX® Mice Models
B6SJL-Tg(SOD1*G93A)1Gur/J (Stock Number 002726)
These transgenics carry a high copy number of a mutant allele human SOD1 containing the Gly93 —>Ala (G93A) substitution (often referred to as G1H). Due to loss of motor neurons in the spinal cord, hemizygous transgenics become paralyzed in one or more limbs and die by the time they are four to five months old.
Reference
Gurney ME, Pu H, Chiu AY, Daly Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng HX, et al. 1994. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264:1772-5.
B6SJL-Tg(SOD1*G93A)dl1Gur/J (Stock Number 002300)
These transgenics carry a variant of the human Superoxide dismutase-1 gene (glycine to alanine at position 93). They have a lower transgene copy number and develop symptoms later than do mutants of the original strain mentioned above (B6SJL-Tg(SOD1-G93A)1Gur/J, Stock Number 002726). They become paralyzed in one or more limbs when they are around six to seven months old and die four to six weeks later.
Reference
Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng HX, et al. 1994. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264:1772-5.
B6.BKS-Ighmbp2nmd-2J/J (Stock Number 002521)
The phenotypes of nmd mutants are very similar to those in human ALS, SMA, and SMARD1. The responsible mutation is a defect in the immunoglobulin S-mu binding protein 2 (Ighmbp2) gene. Mutants are easily identifiable by the time they are two weeks old. Paralysis usually begins in the hindlimbs and progresses to the forelimbs. Balance
is not affected. Most homozygotes die by the time they are four weeks old. Heterozygotes are phenotypically and histologically normal.
References
Cook SA, Johnson KR, Bronson RT, Davisson MT. 1995. Neuromuscular degeneration (nmd): a mutation on mouse Chromosome 19 that causes motor neuron degeneration. Mamm Genome 6 187-91.
Cox GA, Mahaffey CL, Frankel WN 1998. Identification of the mouse neuromuscular
degeneration gene and mapping of a second site suppressor allele. Neuron 21:1327-37.
Grohmann K, Rossoll W, Kobsar I, Holtmann B, Jablonka S, Wessig C, Stoltenburg-
Didinger G, Fischer U, Hubner C, Martini R, Sendtner M. 2004. Characterization of
Ighmbp2 in motor neurons and implications for the pathomechanism in a mouse
model of human spinal muscular atrophy with respiratory distress type 1 (SMARD1).
Hum Mol Genet 13:2031-42.
Maddatu TP, Garvey SM, Schroeder DG, Hampton TG, Cox GA. 2004. Transgenic rescue of neurogenic atrophy in the nmd mouse reveals a role for Ighmbp2 in dilated cardiomyopathy. Hum Mol Genet 13:1105-15
B6.Cg-Tg(SOD1*G93A)1Gur/J (Stock Number 004435)
The transgenic insert carries a high copy number of the mutant allele human SOD1 containing the Gly93 -->Ala (G93A) substitution. 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.
Reference
Gurney ME; Pu H; Chiu AY; Dal Canto MC; Polchow CY; Alexander DD; Caliendo J; Hentati A; Kwon YW; Deng HX; Chen W; Zhai P; Sufit RL; Siddique T. 1994. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation [see comments] [published erratum appears in Science 1995 Jul 14;269(5221):149] Science 264(5166):1772-5.
JAX® Mice for Amyotrophic Lateral Sclerosis
See a complete list of JAX® Mice for amyotrophic lateral sclerosis research.
