Influence of the Lurcher mutation on myosin heavy chain expression in skeletal and cardiac muscles.

Abstract

This study evaluated the influence of Lurcher mutation, characterized by degeneration of cerebellar Purkinje cells, granule cells, and inferior olive neurons, on cardiac and skeletal muscles: one respiratory (diaphragm, Dia), three masticatory (anterior temporalis, AT; masseter superficialis, MS and anterior digastric, AD), one hind limb (soleus, S), entire tongue (T), and one cardiac (ventricle, V) muscles. Body and muscle weight, muscle protein content, and myosin heavy chain (MHC) isoforms relative expression were then compared in Lurcher mutant mice vs. normal, according to sex. Male body weight was always greater than female one, but there was no specific muscle difference in females, except for T relative weight which was greater in normal females. Muscle protein concentration was greater in normal males except for AD and T in which it was lower. Lurcher mutant mice showed a reduced whole body growth but no specific muscle atrophy (except in male AT), and a global decrease in muscle protein content which made muscles more fragile (except in female Dia and male T, in which it was greater). Lurcher mutation induced a global reduction of muscle protein concentration whereas a general influence of sex could not be disclosed. Concerning MHC relative composition, all the muscles were fast-twitch: Dia, AT, MS, AD, S, and T predominantly expressed the fast type 2 MHC isoforms, except female S, whereas V contained only MHC alpha, also a fast MHC. Female muscles were slower than male ones and classification of muscles in terms of shortening velocity was comparable in normal male and female. In other respects, male Lurcher mutant muscles were slower and consequently more fatigue resistant than normal, except T which became faster and less fatigue resistant. On the contrary, in female mutants, only the Dia was slower than normal one, MS and AD were comparable to normal ones and finally, AT, S, and T were faster than normal ones. It should be noted that a developmental MHC (neonatal) was present in Lurcher AD. Motor control, which influences muscle structure, is altered in Lurcher mutant and could be one of the causal factor of the fast-to-slow MHC switches observed in some mutant muscles. It seems therefore that cerebellar Purkinje cells, granule cells, and inferior olive neurons are very important in maintaining the structural integrity of both cardiac and skeletal muscle, and their degeneration is accompanied by important muscles modifications. J. Cell. Biochem. Suppl. 36: 222-231, 2001.