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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Genetic modifiers that aggravate the neurological phenotype of the wobbler mouse.

The autosomal recessive mutation wobbler of the mouse (phenotype WR; genotype wr/wr) causes muscular atrophy due to motoneuron degeneration with 100% penetrance on the standard Mus musculus laboratorius C57BL/6J background. In inter- and backcrosses with M. m. castaneus strain CAST/EI we have observed a variability in the severity of neurological symptoms. Approximately 15% of the WR (wr/wr) CAST/B6 hybrids were modified wobbler (WR*) mice defined by an aggravated neuromuscular phenotype with hindlimbs severely affected in addition to forelimbs. Histologically the overt WR* phenotype was paralleled by a caudally extended neurodegeneration in the ventral horn of the spinal cord with severe astrogliosis, and levels of acetylcholine receptor alpha-subunit mRNA in leg muscle much higher than in standard WR mice. Segregation analysis, using 68 polymorphic autosomal markers in a whole genome scan, revealed a major modifier gene locus, termed wrmod1, on chromosome 14. Individual recombination events in chromosome 14 consomic mice narrowed the wrmod1 candidate region to a 29 cM interval between D14MIT154 and D14MIT105, a region homologous to human chromosome 13q. Our analysis provides access to genes that modify neurodegeneration, the human counterparts of which may be responsible for the variable expression of hereditary spinal muscular atrophies.[1]


  1. Genetic modifiers that aggravate the neurological phenotype of the wobbler mouse. Ulbrich, M., Schmidt, V.C., Ronsiek, M., Mussmann, A., Bartsch, J.W., Augustin, M., Jockusch, H., Schmitt-John, T. Neuroreport (2002) [Pubmed]
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