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Hum Mol Genet. 2017 Jan 1;26(1):65-78. doi: 10.1093/hmg/ddw368.

Lamina-associated polypeptide 1 is dispensable for embryonic myogenesis but required for postnatal skeletal muscle growth.

Author information

1
Department of Medicine.
2
Department of Pathology and Cell Biology, College of Physicians & Surgeons, Columbia University, New York, NY, USA.
3
Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4
Department of Neurology.
5
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.

Abstract

Lamina-associated polypeptide 1 (LAP1) is an integral protein of the inner nuclear membrane that has been implicated in striated muscle maintenance. Mutations in its gene have been linked to muscular dystrophy and cardiomyopathy. As germline deletion of the gene encoding LAP1 is perinatal lethal, we explored its potential role in myogenic differentiation and development by generating a conditional knockout mouse in which the protein is depleted from muscle progenitors at embryonic day 8.5 (Myf5-Lap1CKO mice). Although cultured myoblasts lacking LAP1 demonstrated defective terminal differentiation and altered expression of muscle regulatory factors, embryonic myogenesis and formation of skeletal muscle occurred in both mice with a Lap1 germline deletion and Myf5-Lap1CKO mice. However, skeletal muscle fibres were hypotrophic and their nuclei were morphologically abnormal with a wider perinuclear space than normal myonuclei. Myf5-Lap1CKO mouse skeletal muscle contained fewer satellite cells than normal and these cells had evidence of reduced myogenic potential. Abnormalities in signalling pathways required for postnatal hypertrophic growth were also observed in skeletal muscles of these mice. Our results demonstrate that early embryonic depletion of LAP1 does not impair myogenesis but that it is necessary for postnatal skeletal muscle growth.

PMID:
27798115
PMCID:
PMC6075563
DOI:
10.1093/hmg/ddw368
[Indexed for MEDLINE]
Free PMC Article

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