Testing of SHIRPA, a mouse phenotypic assessment protocol, on Dmd(mdx) andDmd(mdx3cv) dystrophin-deficient mice

The SHIRPA protocol was proposed as a rapid, comprehensive screening method for qualitatively abnormal phenotypes in the mouse (Rogers et al., Mamm Ge nome 8, 711, 1997). This screening technique is currently being used to ide ntify mutants induced by N-ethylnitrosourea (ENU) mutagenesis (Brown and No lan, Hum Mol Genet 7, 1627, 1998). SHIRPA can be used to identify mutants w ith neuromuscular abnormalities, but the sensitivity of the protocol is unk nown. We tested two dystrophin-deficient mutants Dmd(mdx) and Dmd(mdx3cv), both of which are indistinguishable from wild-type by a simple visual asses sment, at different ages, using the primary screen of the SHIRPA protocol, The most dramatic observation was that both Dmd(mdx) and Dmd(mdx3cv) mice s howed extreme fatigue after testing, while mice from the same C57BL strains appeared unaffected. Each strain of dystrophin-deficient mice showed a dif ferent profile in locomotor activity and deficiencies in the wire maneuver, righting reflex, and negative geotaxis tests. Furthermore, the wire maneuv er test indicated an earlier onset of muscular impairment in Dmd(mdx) than Dmd(mdx3cv) mice, These data suggest that the SHIRPA primary screen is effe ctive not only in identifying subtle neuromuscular mutants, but also in dis tinguishing qualitative differences between mutants with neuromuscular abno rmalities.