Retinoic acid rescues inner ear defects in Hoxa1 deficient mice

Nat Genet. 2001 Sep;29(1):34-9. doi: 10.1038/ng702.

Abstract

Little is known about the genetic pathways involved in the early steps of inner ear morphogenesis. Hoxa1 is transiently expressed in the developing hindbrain; its targeted inactivation in mice results in severe abnormalities of the otic capsule and membranous labyrinth. Here we show that a single maternal administration of a low dose of the vitamin A metabolite retinoic acid is sufficient to compensate the requirement for Hoxa1 function. It rescues cochlear and vestibular defects in mutant fetuses without affecting the development of the wildtype fetuses. These results identify a temporal window of susceptibility to retinoids that is critical for mammalian inner ear specification, and provide the first evidence that a subteratogenic dose of vitamin A derivative can be effective in rescuing a congenital defect in the mammalian embryo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Congenital Abnormalities / prevention & control*
  • Ear, Inner / abnormalities*
  • Female
  • Homeodomain Proteins / genetics*
  • Maternal Exposure
  • Mice
  • Mice, Knockout
  • Pregnancy
  • Rhombencephalon / drug effects
  • Rhombencephalon / embryology
  • Transcription Factors / genetics*
  • Tretinoin / pharmacology*

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • homeobox A1 protein
  • Tretinoin