The Enamel Phenotype in Homozygous Fam83h Truncation Mice
Journal
Molecular Genetics and Genomic Medicine
Journal Volume
7
Journal Issue
6
Pages
e724
Date Issued
2019
Author(s)
Abstract
BACKGROUND: Truncation FAM83H mutations cause human autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI), an inherited disorder characterized by severe hardness defects in dental enamel. No enamel defects were observed in Fam83h null mice suggesting that Fam83h truncation mice would better replicate human mutations. METHODS: ) expressing a truncated FAM83H protein (amino acids 1-296), which recapitulated the ADHCAI-causing human FAM83H p.Tyr297* mutation. RESULTS: enamel organ, including ameloblasts, and enamel matrices at sequential stages of amelogenesis exhibited comparable morphology without overt abnormalities, except irregular and less evident ameloblast Tomes' processes in specific areas. CONCLUSIONS: (p.Tyr297*) mice displayed obvious enamel malformations, we conclude that FAM83H truncation mutations causing ADHCAI in humans disturb amelogenesis through a neomorphic mechanism, rather than haploinsufficiency.
SDGs
Publisher
Wiley-Blackwell
Type
journal article