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

This study evaluated the influence of Lurcher mutation, characterized by de generation of cerebellar Purkinje cells, granule cells, and inferior olive neurons, an cardiac and skeletal muscles: one respiratory (diaphragm, Dia), three masticatory (anterior temporalis, AT; masseter superficialis, MS and anterior digastric, AD) ne hind limb (soleus, S), entire tongue (T), and o ne cardiac (ventricle, V)muscles. Body and muscle weight, muscle protein co ntent, and myosin heavy chain (MHC) isoforms relative expression were then compared in Lurcher mutant mice vs. normal, according to sea. Male body wei ght was always greater than female one, but there was no specific muscle di fference in females, except for T relative weight which was greater in norm al 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 w hole body growth hut 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 genera l influence of sex could not be disclosed. Concerning MHC relative composit ion, all the muscles were fast-twitch: Bia, AT, MS, AD, S, and T predominan tly expressed the fast type 2 MHC isoforms, except female SI whereas V cont ained only MHC cr, also a fast MHC. Female muscles were slower than male on es and classification of muscles in terms of shortening velocity was compar able in normal male and female. In other respects, male Lurcher mutant musc les were slower and consequently more fatigue resistant than normal, except T which became faster and less fatigue resistant. On the contrary, in fema le mutants, only the Dia was slower than normal one, MS and AD were compara ble 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 Lurch er AD. Motor control, which influences muscle structure. is altered in Lurc her mutant and could be one of the causal factor of the fast-to-slow MHC sw itches observed in some mutant muscles. It seems therefore that cerebellar Purkinje cells, granule cells, and inferior olive neurons are very importan t in maintaining the structural integrity of both cardiac and skeletal musc le, and their degeneration is accompanied by important muscles modification s, (C) 2001 Wiley-Liss, Inc.