title: A mutation in the enamelin gene in a mouse model.
abstract: Amelogenesis imperfecta is an inherited disorder affecting tooth enamel formation. We previously isolated a mouse strain with an amelogenesis imperfecta phenotype (ATE1 mice) from a dominant ethylnitrosourea screen and mapped the disease-causing defect to a 9-cM region of mouse chromosome 5. In the current study, we tested the hypothesis that there is a mutation in enamelin (ENAM) or ameloblastin (AMBN), both of which are located within the linkage region, by sequencing these two candidate genes. Analysis of our data shows that the amelogenesis imperfecta phenotype is linked to a C > T transition in exon 8 of the enamelin gene. The mutation predicts a C826T transition, which is present in the enamelin transcript and changes the glutamine (Gln) codon at position 176 into a premature stop codon (Gln176X). Conversely, no mutation could be detected in the ameloblastin gene. These results define the ATE1 mice as a model for local hypoplastic autosomal-dominant amelogenesis imperfecta (AIH2), which is caused by enamelin truncation mutations in humans.
authors.affiliation: Department of Prosthetic Dentistry, University Medical Center, Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. seedorf@uke.uni-hamburg.de
authors.forename: H
authors.initials: H
authors.lastname: Seedorf
authors.forename: M
authors.initials: M
authors.lastname: Klaften
authors.forename: F
authors.initials: F
authors.lastname: Eke
authors.forename: H
authors.initials: H
authors.lastname: Fuchs
authors.forename: U
authors.initials: U
authors.lastname: Seedorf
authors.forename: M
authors.initials: M
authors.lastname: Hrabe de Angelis
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D000818:Animals; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D003746:Dental Enamel Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005799:Genes, Dominant; D008040:Genetic Linkage; D005838:Genotype; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
chemical_list: C490890:Ambn protein, mouse; D018389:Codon, Nonsense; D003746:Dental Enamel Proteins; C038456:tuftelin