Amelogenesis imperfecta in a new animal model--a mutation in chromosome 5 (human 4q21).
Candidate genes for amelogenesis imperfecta (AI) and dentinogenesis imperfecta (DI) are located on 4q21 in humans. We tested our hypothesis that mutations in the portion of mouse chromosome 5 corresponding to human chromosome 4q21 would cause enamel and dentin abnormalities. Male C3H mice were injected with ethylnitrosourea (ENU). Within a dominant ENU mutagenesis screen, a mouse mutant was isolated with an abnormal tooth enamel (ATE) phenotype. The structure and ultrastructure of teeth were studied. The mutation was located on mouse chromosome 5 in an interval of 9 cM between markers D5Mit18 and D5Mit10. Homozygotic mutants showed total enamel aplasia with exposed dentinal tubules, while heterozygotic mutants showed a significant reduction in enamel width. Dentin of mutant mice showed a reduced content of mature collagen cross-links. We were able to demonstrate that a mutation on chromosome 5 corresponding to human chromosome 4q21 can cause amelogenesis imperfecta and changes in dentin composition.
Department of Prosthetic Dentistry, University Hospital Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.
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Seedorf
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Springer
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Grundner-Culemann
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Albers
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Reis
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Fuchs
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Hrabe de Angelis
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Açil
D000567:Amelogenesis Imperfecta / Q000235:genetics*; D000818:Animals; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004252:DNA Mutational Analysis; D003743:Dental Enamel / Q000473:pathology; D003746:Dental Enamel Proteins / Q000235:genetics; D003804:Dentin / Q000473:pathology*; D004195:Disease Models, Animal; D005038:Ethylnitrosourea; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains / Q000235:genetics*; D016296:Mutagenesis; D009153:Mutagens
D003746:Dental Enamel Proteins; D009153:Mutagens; D005038:Ethylnitrosourea