title: A new missense mutation in the paired domain of the mouse Pax3 gene.
abstract: Mice with dominant white spotting occurred spontaneously in the C3.NSY-(D11Mit74-D11Mit229) strain. Linkage analysis indicated that the locus for white spotting was located in the vicinity of the Pax3 gene on chromosome 1. Crosses of white-spotted mice showed that homozygosity for the mutation caused tail and limb abnormalities and embryonic lethality as a result of exencephaly; these phenotypes were analogous to those found in other Pax3 mutants. Sequence analysis identified a missense point mutation (c.101G>A) in exon 2 of Pax3 that resulted in a methionine to isoleucine conversion at amino acid 62 of the PAX3 protein. This mutation site was located in the N-terminal HTH (helix-turn-helix) motif of the paired domain of Pax3, which is necessary for binding to DNA and is highly conserved in vertebrate species. Alteration of DNA binding affinity was responsible for embryonic lethality in homozygotes and white spotting in heterozygotes. We named the mutant allele as Pax3Sp-Nag. The C3H/HeN-Pax3Sp-Nagstrain may be useful for analyzing the function of Pax3 as a new model of the human disease, Waardenburg Syndrome.
authors.affiliation: Division of Experimental Animals, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Tamio
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Division of Experimental Animals, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Maegawa
authors.affiliation: Division of Experimental Animals, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Katoh
authors.affiliation: Division of Experimental Animals, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Miyasaka
authors.affiliation: Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Horio
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D019077:Helix-Turn-Helix Motifs / Q000235:genetics; D006801:Humans; D007532:Isoleucine; D008715:Methionine; D008815:Mice, Inbred Strains; D020125:Mutation, Missense; D000072041:PAX3 Transcription Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D017354:Point Mutation; D011485:Protein Binding; D000072417:Protein Domains / Q000235:genetics*; D014849:Waardenburg Syndrome / Q000235:genetics*
chemical_list: D000072041:PAX3 Transcription Factor; D007532:Isoleucine; C068686:Pax3 protein, mouse; D004247:DNA; D008715:Methionine
keywords: Pax3 gene; embryonic lethal; missense mutation; mouse; white spotting