Cell
Volume 71, Issue 3, 30 October 1992, Pages 369-382
Journal home page for Cell

Article
Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death

https://doi.org/10.1016/0092-8674(92)90507-9Get rights and content

Abstract

The Myf-5 gene, a member of the myogenic basic HLH factor family, has been inactivated in mice after homologous recombination in ES cells. Mice lacking Myf-5 were unable to breathe and died immediately after birth, owing to the absence of the major distal part of the ribs. Other skeletal abnormalities, except for complete ossification of the sternum, were not apparent. Histological examination of skeletal muscle from newborn mice revealed no morphological abnormalities. Northern blot analysis demonstrated normal levels of muscle-specific mRNAs including MyoD, myogenin, and Myf-6. However, the appearance of myotomal cells in early somites was delayed by several days. These results suggest that while Myf-5 plays a crucial role in the formation of lateral sclerotome derivatives, Myf-5 is dispensable for the development of skeletal muscle, perhaps because other members of the myogenic HLH family substitute for Myf-5 activity.

References (71)

  • M.E. Pownall et al.

    Sequential activation of three myogenic regulatory genes during somite morphogenesis in quail embryos

    Dev. Biol.

    (1992)
  • E.J. Sanders et al.

    Extracellular matrix synthesis is required for the movement of sclerotome and neural crest cells on collagen

    Differentiation

    (1988)
  • U. Seidel et al.

    Identification of the functional promoter regions in the human gene encoding the myosin alkali light chains MLC1 and MLC3 of fast skeletal muscle

    J. Biol. Chem.

    (1989)
  • M.-A. Teillet et al.

    Consequences of neural tube and notochord excision on the development of the peripheral nervous system in the chick embryo

    Dev. Biol.

    (1983)
  • M.J. Thayer et al.

    Positive autoregulation of the myogenic determination gene MyoD1

    Cell

    (1989)
  • K.R. Thomas et al.

    Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells

    Cell

    (1987)
  • W.E. Wright

    Muscle basic helix-loop helix proteins and the regulation of myogenesis

    Curr. Opin. Gen. Dev.

    (1992)
  • W.E. Wright et al.

    Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD

    Cell

    (1989)
  • H.-H. Arnold et al.

    Myogenic control genes in vertebrates

  • C. Auffray et al.

    Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA

    Eur. J. Biochem.

    (1980)
  • D. Bader et al.

    Immunochemical analysis of myosin heavy chain during avian myogenesis in vivo and in vitro

    J. Cell Biol.

    (1982)
  • J.D. Bancroft et al.

    Theory and Practice of Histological Techniques

    (1990)
  • E. Bober et al.

    The muscle regulatory gene, Myf-6, has a biphasic pattern of expression during early mouse development

    J. Cell Biol.

    (1991)
  • A. Bradley

    Production and Analysis of Chimeric Mice

    (1987)
  • T. Braun et al.

    The four human muscle regulatory helix-loop-helix proteins Myf-3-Myf-6 exhibit similar hetero-dimerization and DNA binding properties

    Nucl. Acids Res.

    (1991)
  • T. Braun et al.

    Differential expression of myogenic determination genes in muscle cells: possible autoactivation by the Myf gene products

    EMBO J.

    (1989)
  • T. Braun et al.

    A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T12 fibroblasts

    EMBO J.

    (1989)
  • T. Braun et al.

    Myf-6, a new member of the human gene family of myogenic determination factors: evidence for a gene cluster on chromosome 12

    EMBO J.

    (1990)
  • T. Braun et al.

    Transcriptional activation domain of the muscle-specific gene-regulatory protein Myf-5

    Nature

    (1990)
  • T. Braun et al.

    Baculovirus-expressed myogenic determination factors require E12 complex formation for binding to the myosin-light-chain enhancer

    Eur. J. Biochem.

    (1991)
  • T. Braun et al.

    Inhibition of muscle differentiation by the adenovirus E1a protein: repression of the transcriptional activating function of the HLH protein Myf-5

    Genes Dev.

    (1992)
  • T.J. Brennan et al.

    Mutagenesis of the myogenin basic region identifies an ancient protein motif critical for activation of myogenesis

  • M.H. Brooke et al.

    Three “myosin adenosine triphosphatase” systems: the nature of their pH lability and sulfhydryl dependence

    J. Histochem. Cytochem.

    (1970)
  • F. Charles de la Brousse et al.

    Localized expression of a myogenic regulatory gene, qmf1, in the somite dermatome of avian embryos

    Genes Dev.

    (1990)
  • D.G. Edmondson et al.

    A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program

    Genes Dev.

    (1989)
  • Cited by (600)

    View all citing articles on Scopus

    Present address: McMaster University, Institute for Molecular Biology and Biotechnology, Hamilton, Ontario, Canada, L8S 4K1.

    View full text