title: Point mutation of Hoxd12 in mice.
abstract: OBJECTIVE
  Genes of the HoxD cluster play a major role in vertebrate limb development, and changes that modify the Hoxd12 locus affect other genes also, suggesting that HoxD function is coordinated by a control mechanism involving multiple genes during limb morphogenesis. In this study, mutant phenotypes were produced by treatment of mice with a chemical mutagen, N-ethyl-N-nitrosourea (ENU). We analyzed mutant mice exhibiting the specific microdactyly phenotype and examined the genes affected.
  
  
  METHODS
  We focused on phenotype characteristics including size, bone formation, and digit morphology of ENU-induced microdactyly mice. The expressions of several molecules were analyzed by genome-wide screening and quantitative real-time PCR to define the affected genes.
  
  
  RESULTS
  We report on limb phenotypes of an ENU-induced A-to-C mutation in the Hoxd12 gene, resulting in alanine-to-serine conversion. Microdactyly mice exhibited growth defects in the zeugopod and autopod, shortening of digits, a missing tip of digit I, limb growth affected, and dramatic increases in the expressions of Fgf4 and Lmx1b. However, the expression level of Shh was not changed in Hoxd12 point mutated mice.
  
  
  CONCLUSIONS
  These results suggest that point mutation rather than the entire deletion of Hoxd12, such as in knockout and transgenic mice, causes the abnormal limb phenotype in microdactyly mice. The precise nature of the spectrum of differences requires further investigation.
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, College of Dentistry, Yonsei University, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Korea.
authors.forename: Kyoung-Won
authors.initials: KW
authors.lastname: Cho
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Cho
authors.forename: Kyu-Hyuk
authors.initials: KH
authors.lastname: Cho
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Song
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Jung
mesh_terms: D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005038:Ethylnitrosourea / Q000633:toxicity; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D017880:Limb Deformities, Congenital / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009153:Mutagens / Q000633:toxicity; D017354:Point Mutation; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; C490943:Hoxd12 protein, mouse; D009153:Mutagens; D014157:Transcription Factors; D004247:DNA; D005038:Ethylnitrosourea