Fam83h null mice support a neomorphic mechanism for human ADHCAI

Molecular Genetics & Genomic Medicine
S WangJ P Simmer

Abstract

Truncation mutations in FAM83H (family with sequence similarity 83, member H) cause autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI), but little is known about FAM83H function and the pathogenesis of ADHCAI. We recruited three ADHCAI families and identified two novel (p.Gln457*; p.Lys639*) and one previously documented (p.Q452*) disease-causing FAM83H mutations. We generated and characterized Fam83h-knockout/lacZ-knockin mice. Surprisingly, enamel thickness, density, Knoop hardness, morphology, and prism patterns were similar in Fam83h (+/+), Fam83h (+/-), and Fam83h (-/-) mice. The histology of ameloblasts in all stages of development, in both molars and incisors, was virtually identical in all three genotypes and showed no signs of pathology, although the Fam83h (-/-) mice usually died after 2 weeks and rarely survived to 7 weeks. LacZ expression in the knockin mice was used to report Fam83h expression in the epithelial tissues of many organs, notably in skin and hair follicles, which manifested a disease phenotype. Pull-down studies determined that FAM83H dimerizes through its N-terminal phospholipase D-like (PLD-like) domain and identified potential FAM83H interacting proteins. Casein kinase 1 (CK1) interac...Continue Reading

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Citations

Sep 30, 2016·Scientific Reports·Takahisa KugaTakeshi Tomonaga
Jul 7, 2017·PloS One·Wushuang HuangYaling Song
Jun 28, 2018·Oral Diseases·Nunthawan NowwaroteVorasuk Shotelersuk
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Oct 10, 2020·Journal of Dental Research·S K WangJ C C Hu
Dec 2, 2020·International Journal of Molecular Sciences·Keigo YoshizakiYuko Oda
Dec 12, 2020·The Biochemical Journal·Luke J Fulcher, Gopal P Sapkota

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Methods Mentioned

BETA
PCR
genotyping
scanning electron microscopy
pull down
affinity purification
immunoprecipitation
Pull
Exome Sequencing
dissection
affinity

Software Mentioned

ELAND
Ozgene
SAM
SPRING
SPRING ON ‐ LINE

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