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Biochem Biophys Res Commun. 2014 Jan 3;443(1):313-20. doi: 10.1016/j.bbrc.2013.11.108. Epub 2013 Dec 2.

Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes.

Author information

1
Department of Anatomy, Chang Gung University Medical College, Taiwan.
2
Transgenic Mouse Core Laboratory, Chang Gung University, Taiwan.
3
Department of Anatomy, Chang Gung University Medical College, Taiwan; Transgenic Mouse Core Laboratory, Chang Gung University, Taiwan; Molecular Medicine Research Center, Chang Gung University, Taiwan. Electronic address: ouyang@mail.cgu.edu.tw.

Abstract

Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species. The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity.

KEYWORDS:

Muscular dystrophy; Nebulin; Pinin; Slow type fiber gene

PMID:
24309110
DOI:
10.1016/j.bbrc.2013.11.108
[Indexed for MEDLINE]

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