title: The synpolydactyly homolog (spdh) mutation in the mouse -- a defect in patterning and growth of limb cartilage elements.
abstract: We have investigated the recessive mouse mutant synpolydactyly homolog (spdh) as a model for human synpolydactyly (SPD). As in human SPD, the spdh phenotype consists of central polydactyly, syndactyly and brachydactyly and is caused by the expansion of a polyalanine encoding repeat in the 5' region of the Hoxd13 gene. We performed a detailed phenotypic and functional analysis of spdh/spdh embryos using skeletal preparations, histology, in situ hybridization, BrdU labeling of proliferating cells, and in vitro expression studies. The absence of normal phalangeal joints and the misexpression of genes involved in joint formation demonstrate a role for Hox-genes in joint patterning. The spdh mutation results in abnormal limb pattering, defective chondrocyte differentiation, and in a drastic reduction in proliferation. Abnormal chondrocyte differentiation and proliferation persisted after birth and correlated with the expression of the mutant Hoxd13 and other Hox-genes during late-embryonic and postnatal growth.
authors.affiliation: Max-Planck-Institut fur Molekulare Genetik, Berlin, Germany.
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Albrecht
authors.forename: Georg C
authors.initials: GC
authors.lastname: Schwabe
authors.forename: Sigmar
authors.initials: S
authors.lastname: Stricker
authors.forename: Annett
authors.initials: A
authors.lastname: Böddrich
authors.forename: Erich E
authors.initials: EE
authors.lastname: Wanker
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
mesh_terms: D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism; D019556:COS Cells; D002356:Cartilage / Q000196:embryology*; D002454:Cell Differentiation; D002455:Cell Division; D019902:Chondrocytes / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004195:Disease Models, Animal; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010641:Phenotype; D017689:Polydactyly / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors
chemical_list: D018076:DNA, Complementary; D018398:Homeodomain Proteins; C084118:Hoxd13 protein, mouse; D014157:Transcription Factors; D001973:Bromodeoxyuridine