Retinoic acid rescues inner ear defects in Hoxa1 deficient mice

Citation
M. Pasqualetti et al., Retinoic acid rescues inner ear defects in Hoxa1 deficient mice, NAT GENET, 29(1), 2001, pp. 34-39
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
NATURE GENETICS
ISSN journal
1061-4036 → ACNP
Volume
29
Issue
1
Year of publication
2001
Pages
34 - 39
Database
ISI
SICI code
1061-4036(200109)29:1<34:RARIED>2.0.ZU;2-N
Abstract
Little is known about the genetic pathways involved in the early steps of i nner ear morphogenesis. Hoxa1 is transiently expressed in the developing hi ndbrain; its targeted inactivation in mice results in severe abnormalities of the otic capsule and membranous labyrinth(1). 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 re scues cochlear and vestibular defects in mutant fetuses without affecting t he development of the wildtype fetuses. These results identify a temporal w indow of susceptibility to retinoids that is critical for mammalian inner e ar specification, and provide the first evidence that a subteratogenic dose of vitamin A derivative can be effective in rescuing a congenital defect i n the mammalian embryo.