The SHIRPA protocol was proposed as a rapid, comprehensive screening method for qualitatively abnormal phenotypes in the mouse (Rogers et al., Mamm Genome 8, 711, 1997). This screening technique is currently being used to identify mutants induced by N-ethylnitrosourea (ENU) mutagenesis (Brown and Nolan, Hum Mol Genet 7, 1627, 1998). SHIRPA can be used to identify mutants with neuromuscular abnormalities, but the sensitivity of the protocol is unknown. We tested two dystrophin-deficient mutants Dmd mdx and Dmd mdx3cv , both of which are indistinguishable from wild-type by a simple visual assessment, at different ages, using the primary screen of the SHIRPA protocol. The most dramatic observation was that both Dmd mdx and Dmd mdx3cv mice showed extreme fatigue after testing, while mice from the same C57BL strains appeared unaffected. Each strain of dystrophin-deficient mice showed a different profile in locomotor activity and deficiencies in the wire maneuver, righting reflex, and negative geotaxis tests. Furthermore, the wire maneuver test indicated an earlier onset of muscular impairment in Dmd mdx than Dmd mdx3cv mice. These data suggest that the SHIRPA primary screen is effective not only in identifying subtle neuromuscular mutants, but also in distinguishing qualitative differences between mutants with neuromuscular abnormalities.
Mammalian Genome – Springer Journals
Published: Feb 13, 2014
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