RRC ID 47775
Author Ohno T, Maegawa T, Katoh H, Miyasaka Y, Suzuki M, Kobayashi M, Horio F.
Title A new missense mutation in the paired domain of the mouse Pax3 gene.
Journal Exp Anim
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-Nag strain may be useful for analyzing the function of Pax3 as a new model of the human disease, Waardenburg Syndrome.
Volume 66(3)
Pages 245-250
Published 2017-8-5
DOI 10.1538/expanim.17-0013
PMID 28381738
PMC PMC5543245
MeSH Alleles Amino Acid Sequence / genetics Animals DNA / metabolism Disease Models, Animal Helix-Turn-Helix Motifs / genetics Humans Isoleucine Methionine Mice, Inbred Strains Mutation, Missense* PAX3 Transcription Factor / chemistry PAX3 Transcription Factor / genetics* PAX3 Transcription Factor / metabolism PAX3 Transcription Factor / physiology Point Mutation* Protein Binding Protein Domains / genetics* Waardenburg Syndrome / genetics*
IF 1.574
Times Cited 0
Mice RBRC01934