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PMID: 9813102 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Dystrophic muscle in mice chimeric for expression of alpha5 integrin.

The Journal of cell biology ·Vol. 143 ·No. 3 ·1998-11-02 ·Pages 849-59

Taverna D, Disatnik MH, Rayburn H, Bronson RT, Yang J, Rando TA, Hynes RO

Abstract

alpha5-deficient mice die early in embryogenesis (). To study the functions of alpha5 integrin later in mouse embryogenesis and during adult life we generated alpha5 -/-;+/+ chimeric mice. These animals contain alpha5-negative and positive cells randomly distributed. Analysis of the chimerism by glucose- 6-phosphate isomerase (GPI) assay revealed that alpha5 -/- cells contributed to all the tissues analyzed. High contributions were observed in the skeletal muscle. The perinatal survival of the mutant chimeras was lower than for the controls, however the subsequent life span of the survivors was only slightly reduced compared with controls (). Histological analysis of alpha5 -/-;+/+ mice from late embryogenesis to adult life revealed an alteration in the skeletal muscle structure resembling a typical muscle dystrophy. Giant fibers, increased numbers of nuclei per fiber with altered position and size, vacuoli and signs of muscle degeneration-regeneration were observed in head, thorax and limb muscles. Electron microscopy showed an increase in the number of mitochondria in some muscle fibers of the mutant mice. Increased apoptosis and immunoreactivity for tenascin-C were observed in mutant muscle fibers. All the alterations were already visible at late stages of embryogenesis. The number of altered muscle fibers varied in different animals and muscles and was often increased in high percentage chimeric animals. Differentiation of alpha5 -/- ES cells or myoblasts showed that in vitro differentiation into myotubes was achieved normally. However proper adhesion and survival of myoblasts on fibronectin was impaired. Our data suggest that a novel form of muscle dystrophy in mice is alpha5-integrin-dependent.

MeSH Terms
Animals Antigens, CD/genetics,physiology Cell Line Chimera Female Integrin alpha5 Mice Mice, Inbred C57BL Mice, Knockout Muscle, Skeletal/embryology,pathology Muscular Dystrophies/embryology,etiology
Chemicals
Antigens, CD Integrin alpha5
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Taverna D
Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Disatnik M H
Rayburn H
Bronson R T
Yang J
Rando T A
Hynes R O
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.143.3.849
Published
1998-11-02
Pages
849-59
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2148145
Subset
IM
Grants
NHLBI NIH HHS · P01 HL41484 · United States
External Links
PubMed source DOI: 10.1083/jcb.143.3.849 PMC Full Text View journal details
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