Myostatin inhibition using mRK35 produces skeletal muscle growth and tubular aggregate formation in wild type and TgACTA1D286G nemaline myopathy mice. Hum Mol Genet 2018 Feb 15;27(4):638-648
Date
01/03/2018Pubmed ID
29293963Pubmed Central ID
PMC5886278DOI
10.1093/hmg/ddx431Scopus ID
2-s2.0-85041501214 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
Nemaline myopathy (NM) is a heterogeneous congenital skeletal muscle disease with cytoplasmic rod-like structures (nemaline bodies) in muscle tissue. While weakness in NM is related to contractile abnormalities, myofiber smallness is an additional abnormality in NM that may be treatable. We evaluated the effects of mRK35 (a myostatin inhibitor developed by Pfizer) treatment in the TgACTA1D286G mouse model of NM. mRK35 induced skeletal muscle growth that led to significant increases in animal bodyweight, forelimb grip strength and muscle fiber force, although it should be noted that animal weight and forelimb grip strength in untreated TgACTA1D286G mice was not different from controls. Treatment was also associated with an increase in the number of tubular aggregates found in skeletal muscle. These findings suggest that myostatin inhibition may be useful in promoting muscle growth and strength in Acta1-mutant muscle, while also further establishing the relationship between low levels of myostatin and tubular aggregate formation.
Author List
Tinklenberg JA, Siebers EM, Beatka MJ, Meng H, Yang L, Zhang Z, Ross JA, Ochala J, Morris C, Owens JM, Laing NG, Nowak KJ, Lawlor MWAuthor
Michael W. Lawlor MD, PhD Adjunct Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ActinsAnimals
Forelimb
Hand Strength
Male
Mice
Mice, Transgenic
Muscle, Skeletal
Myopathies, Nemaline
Myostatin
