B6C3Fe a/a-Eef1a2^wst/J

Stock number: 000182
Research areas: Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Neurobiology Research

Detailed description

Mice homozygous for the wasted spontaneous mutation (Eef1a2^wst) can be recognized at 20 days of age by tremor and uncoordinated body movements. Homozygous mutant mice develop progressive paralysis and do not survive beyond 30 days. They have marked lymphoid hypoplasia in the spleen, thymus, lymph nodes, and peripheral blood. Wasted mice have a severely reduced number of IgA plasma cells in the entire large and small intestines, but the number of such cells in the spleen and the level of serum IgA are normal.

Neuronal degeneration occurs in the brain and spinal cord. Spinal cord abnormalities are preceded by gliosis following along a rostrocaudal gradient. Thoracic/abdominal muscles exhibit a progressive denervation of muscle fibers, with progressive asynchronous retraction of motor nerve terminals. (Newbery HJ, et al. 2005)

Development

The wasted mutation arose spontaneously on the HRS/J background in 1972 and was subsequently maintained by breeding hosts of homozygous ovarian transplants to B6C3Fe-a/a F1 then intercrossing the heterozygous offspring. In 1987 heterozygotes at generation N28F1 were intercrossed to generate embryos for cryopreservation.

Allele

Symbol: Eef1a2^wst
Name: wasted
MGI accession ID: MGI:1857093
Generation method: Spontaneous
Marker symbol: Eef1a2
Marker name: eukaryotic translation elongation factor 1 alpha 2
Chromosome: 2
Strain of origin: HRS/J
Molecular note: The mutation is a 15.8kb deletion that removes the promoter region and first noncoding exon of the gene.
General note: The enzymatic specific activity of ADA (which takes into account the reduced tissue weights of wasted mice) is increased in the spleen and cerebellum but decreased in the thymus of these mutants (J:12932). Wasted mutant mice have marked lymphoid hypoplasia in the spleen, thymus, lymph nodes, and peripheral blood. Wasted mice show some similarities to human ataxia telangiectasia (AT; MIM 208900; human gene, ATM; mouse gene, Atm) (J:6766), but there are also numerous differences. But the mutant mice lack the increased sensitivity of spleen cells to killing by ultraviolet radiation (J:20567), the increased sensitivity of cultured fibroblasts to killing by X or gamma radiation (J:8348, J:13960), and the increased post-irradiation inhibition of DNA synthesis (J:7561) characteristic of AT. In addition, the immunological defects of wasted mice differ considerably from those in human AT (J:8288). Wasted mice have a severely reduced number of IgA plasma cells in the entire large and small intestine, but the level of such cells in spleen and the level of serum IgA are normal (J:7903). The mutants also show an extensive cytokine imbalance of many immunologically relevant gene products (IL5, IL1, IL2, IFNG, and TGFB1) which may trigger the wasted pathogenesis (J:19431). The overlapping similarities between AT and wasted, however, have suggested the possibility that Eef1a2 and Atm may be involved in a common pathway, such as a signal-transduction pathway that regulates protein synthesis (J:48050). In fact Eef1a2ws mice show abnormal expression of the proliferating cellular nuclear antigen (PCNA) in the thymus (J:37955).