title: Postaxial polydactyly in forelimbs of CRABP-II mutant mice.
abstract: The cytoplasmic retinoic acid (RA)-binding protein CRABP-II is expressed widely throughout early morphogenesis in mouse embryo, but its expression becomes more restricted as organogenesis progresses. CRABP-II expression remains strong in the developing limb bud suggesting a role for this protein in limb patterning. Here, we show that the CRABP-II promoter can direct expression of a lacZ transgene in a specific posterior domain during limb bud development. In order to investigate in more detail the role played by CRABP-II in RA signal transduction, we have also generated mice homozygous for a null mutation of this gene. CRABPII-/- mice are viable and fertile but show a developmental defect of the forelimb, specifically an additional, postaxial digit. This digit is generally, but not exclusively, limited to a single forepaw of an individual animal. The penetrance of the phenotype varies according to the genetic background, occurring most frequently on the inbred 129Sv background (50%), less frequently on the C57Bl/6 background (30%) and rarely on the outbred CD1 background (10%). This developmental abnormality implies a role for CRABP-II in normal patterning of the limb.
authors.affiliation: Division of Endocrinology, Hospital for Sick Children, Toronto, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Fawcett
authors.forename: P
authors.initials: P
authors.lastname: Pasceri
authors.forename: R
authors.initials: R
authors.lastname: Fraser
authors.forename: M
authors.initials: M
authors.lastname: Colbert
authors.forename: J
authors.initials: J
authors.lastname: Rossant
authors.forename: V
authors.initials: V
authors.lastname: Giguère
mesh_terms: D000818:Animals; D005552:Forelimb / Q000002:abnormalities*; D015870:Gene Expression; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000187:drug effects / Q000235:genetics; D010641:Phenotype; D017689:Polydactyly / Q000196:embryology / Q000235:genetics*; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin