Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC64
Effects of the murine myostatin mutation on muscle properties depend on the genetic background
A. Lionikas1, A. M. Carroll1, A. Ratkevicius1, L. Bünger2
1. School of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom. 2. Scottish Agricultural College, Edinburgh, Scotland, United Kingdom.
Inhibition of myostatin increases muscle size in mice (2) but the mechanisms (hypertrophy and/or hyperplasia) and extent of the effect varies between different models (3, 4). This variation may stem from the interaction with the genetic background of mouse strain. Studying the effects of myostatin polymorphisms on different genetic backgrounds will aid our understanding of its influence in heterogeneous population such as humans. We examined the effects of the Compact allele of myostatin in two high-growth mouse strains, BEH and DUI, after introgressing the wildtype (+) allele and the Compact (C) allele, respectively by marker assisted selection (1, 3). We analyzed the size of extensor digitorum longus (EDL) and soleus muscles and fibre properties of the latter in BEHC/C, BEHC/+, BEH+/+, as well as DUIC/C, DUIC/+ and DUI+/+ male mice at 70d. Presented values are mean ± SD. For comparisons 2-way ANOVA and t-test were used as appropriate. Weights of the EDL and soleus muscles were higher (P<0.0001 for both) in BEHC/C (27 ± 3.2 mg and 16.6 ± 2.2 mg, respectively; n=16) than in BEH+/+ males (12.3 ± 0.8 mg and 9.8 ± 0.7 mg, n=8). The EDL weight was higher (P<0.05) in DUIC/C (28.7 ± 2.8 mg; n=6) than in the DUI+/+ males (24.3 ±3.3 mg; n=12). Weight of the soleus, however, tended (P=0.07) to be affected inversely between the DUIC/C (18.5 ± 4.1 mg) and the DUI+/+ (22.3 ± 3.7 mg) samples. We examined the underlying mechanisms of interaction between Compact and the genetic background by analyzing the number and cross-section area (CSA) of soleus fibres in ATPase stained histological samples. Total number of fibres was slightly higher in BEHC/C than in BEH+/+ (1063 ± 55, n=6; and 957 ± 96, n=8, respectively; P<0.05). There was no difference, however, between the DUIC/C and DUI+/+ genotypes (1192 ± 70, n=5; 1249 ± 231, n=9). Compact reduced the number of type 1 fibres and increased that of type 2A on the BEH background (type 1: BEH+/+ 471 ± 36 vs BEHC/C 371 ± 58, P<0.01; type 2A: 469 ± 71 vs 667 ± 92, P<0.01), however, no effect was observed on the DUI background (type 1: DUI+/+ 784 ± 67 vs DUIC/C 716 ± 54; type 2A: 360 ± 220 vs 388 ± 76). Compact increased CSA in a dominant manner across fibre types on the BEH background (type 1: BEH+/+ 1304 ± 139 μm2 vs BEHC/C 1672 ± 158 μm2, P<0.001; type 2A: 1454 ± 111 μm2 vs 1932 ±139 μm2, respectively, P<0.001) but induced the opposite effect on the DUI background (type 1: DUI+/+ 1948 ± 323 μm2 vs DUIC/C 1629 ± 284 μm2, P=0.06; type 2A: 2671 ± 427 μm2 vs 1603 ± 412 μm2, respectively, P<0.001). We conclude that the genetic background modified the effect of myostatin, particularly in the soleus which resembles fibre type composition of human postural muscles. These findings suggest that pharmacological or other interventions via myostatin may have variable effects in humans depending on the individual genetic makeup.
Where applicable, experiments conform with Society ethical requirements