Lamina-associated polypeptide 1 is dispensable for embryonic myogenesis but required for postnatal skeletal muscle growth
| Autor: | Howard J. Worman, Robert S. Krauss, Wei Wu, Iván Méndez-López, Mingi Hong, Ji Yeon Shin, Leana Shugol, William T. Dauer, Yuexia Wang, Kurenai Tanji |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Cellular differentiation Biology Muscle Development Muscular Dystrophies Myoblasts 03 medical and health sciences Mice 0302 clinical medicine Conditional gene knockout Genetics medicine Myocyte Animals Muscular dystrophy Muscle Skeletal Molecular Biology Genetics (clinical) Cell Proliferation Regulation of gene expression Mice Knockout Myogenesis Skeletal muscle Gene Expression Regulation Developmental Membrane Proteins Cell Differentiation General Medicine Anatomy Articles medicine.disease Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Myogenic Regulatory Factors Myogenic regulatory factors Female Carrier Proteins 030217 neurology & neurosurgery |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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