Cell
Volume 78, Issue 6, 23 September 1994, Pages 987-1003
Journal home page for Cell

Article
Genetic analysis of RXRα developmental function: Convergence of RXR and RAR signaling pathways in heart and eye morphogenesis

https://doi.org/10.1016/0092-8674(94)90274-7Get rights and content

Abstract

A null mutation was generated in the mouse RXRα gene by targeted disruption. Growth deficiency occurred in heterozygote mice. Null mutants died in utero and displayed myocardial and ocular malformations. These malformations belong to the fetal vitamin A deficiency syndrome, supporting the idea that RXRα is involved in retinoid signaling in vivo. A phenotypic synergy was observed when the RXRα mutation was introduced into RARα or RARγ mutant backgrounds: RXRα null mutants and RXRα+/−RARγ−/− double mutants displayed similar ocular defects, which became more severe in RXRα−/−RARγ+/− and RXRα−/−RARγ−/− mutants. Furthermore, RXRαRAR double mutants exhibited several malformations not seen in single mutants. This functional convergence strongly suggests that RXRαRAR heterodimers mediate retinoid signaling in vivo.

References (56)

  • P. McCaffery et al.

    Changing patterns of the retinoic acid system in the developing retina

    Dev. Biol.

    (1993)
  • P.P. Rumyantsev

    Interrelations of the proliferation and differentiation processes during cardiac myogenesis and regeneration

    Int. Rev. Cytol.

    (1977)
  • N.C. Andrews et al.

    A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells

    Nucl. Acids Res.

    (1991)
  • G. Bedo et al.

    Retinoic acid regulates growth hormone gene expression

    Nature

    (1989)
  • R.B. Blomhoff
  • C.E. Challice et al.

    The architectural development of the early mammalian heart

    Tissue Cell

    (1973)
  • J.L. Coulombre et al.

    Lens development. IV. Size, shape, and orientation

    Invest. Ophthalmol.

    (1969)
  • A.J. Coulombre et al.

    Abnormal organogenesis in the eye

  • H. De Luca

    The vitamin D story: a collaborative effort of basic science and clinical medicine

    FASEB J.

    (1988)
  • R.M. Evans

    The steroid and thyroid hormone receptor superfamily

    Science

    (1988)
  • V. Giguère

    Retinoic acid receptors and cellular retinoid binding proteins: complex interplay in retinoid signaling

    Endocrine Rev.

    (1994)
  • A. Gossler et al.

    Transgenesis by means of blastocyst-derived embryonic stem cell lines

  • E.D. Hay

    Development of the vertebrate cornea

    Int. Rev. Cytol.

    (1980)
  • D.M. Heery et al.

    Efficient transactivation by retinoic acid receptors in yeast requires retinoid X receptors

  • I. Hero

    Optic fissure closure in the normal cinnamon mouse

    Invest. Ophthalmol. Vis. Sci.

    (1990)
  • P. Kastner et al.

    The role of nuclear retinoic acid receptors in the regulation of gene expression

  • M.H. Kaufman

    The Atlas of Mouse Development

    (1992)
  • M.L. Kirby et al.

    Neural crest cells contribute to normal aorticopulmonary septation

    Science

    (1983)
  • Cited by (0)

    View full text