Loss of FAM20A protein induces Amelogenesis Imperfecta in mice
نویسندگان
چکیده
FAM20A is a member of family of related proteins that has been named family with sequence similarity 20 (FAM20) with three members (FAM20A, FAM20B and FAM20C) in mammals. Recently, some studies have reported that patients with Amelogenesis Imperfecta caused by FAM20A mutation displayed several dental phenotypes including hypoplastic enamel, failure of tooth development and gingival hyperplasia. We have reported a transgenic mouse line with a 58-kb fragment deletion that encompasses part of the Fam20a gene and its upstream region shows growth disorder. In the present study, we aimed to clarify how the loss of Fam20a protein influenced the development of dental tissues in the Fam20a-/mouse. The light microscopic study (LM) of paraffin-embedded specimens demonstrated hypoplastic enamel and gingival hyperplasia in the Fam20a-/mice. The LM of ground sections of the mandibles containing teeth showed that there was no enamel covering the coronal dentine. Immunohistochemical study of the mandibles (paraffin-embedded specimens) indicated that Fam20a protein expressed in osteoid tissue and tooth germ of Fam20a+/+ mice, but does not expressed in Fam20a-/mice. In conclusion, this study revealed that the FAM20A protein is required for enamel formation.
منابع مشابه
Further evidence for causal FAM20A mutations and first case of amelogenesis imperfecta and gingival hyperplasia syndrome in Morocco: a case report
BACKGROUND Amelogenesis imperfecta represents a group of developmental conditions, clinically and genetically heterogeneous, that affect the structure and clinical appearance of enamel. Amelogenesis imperfecta occurred as an isolated trait or as part of a genetic syndrome. Recently, disease-causing mutations in the FAM20A gene were identified, in families with an autosomal recessive syndrome as...
متن کاملFAM20A Mutations Can Cause Enamel-Renal Syndrome (ERS)
Enamel-renal syndrome (ERS) is an autosomal recessive disorder characterized by severe enamel hypoplasia, failed tooth eruption, intrapulpal calcifications, enlarged gingiva, and nephrocalcinosis. Recently, mutations in FAM20A were reported to cause amelogenesis imperfecta and gingival fibromatosis syndrome (AIGFS), which closely resembles ERS except for the renal calcifications. We characteriz...
متن کاملA distinctive oral phenotype points to FAM20A mutations not identified by Sanger sequencing
Biallelic FAM20A mutations cause two conditions where Amelogenesis Imperfecta (AI) is the presenting feature: Amelogenesis Imperfecta and Gingival Fibromatosis Syndrome; and Enamel Renal Syndrome. A distinctive oral phenotype is shared in both conditions. On Sanger sequencing of FAM20A in cases with that phenotype, we identified two probands with single, likely pathogenic heterozygous mutations...
متن کاملFAM20A binds to and regulates FAM20C localization
Mutations in the Family with sequence similarity (FAM) 20 gene family are associated with mineralized tissue phenotypes in humans. Among these genes, FAM20A mutations are associated with Amelogenesis Imperfecta (AI) with gingival hyperplasia and nephrocalcinosis, while FAM20C mutations cause Raine syndrome, exhibiting bone and craniofacial/dental abnormalities. Although it has been demonstrated...
متن کاملStructure of Fam20A reveals a pseudokinase featuring a unique disulfide pattern and inverted ATP-binding
Mutations in FAM20A cause tooth enamel defects known as Amelogenesis Imperfecta (AI) and renal calcification. We previously showed that Fam20A is a secretory pathway pseudokinase and allosterically activates the physiological casein kinase Fam20C to phosphorylate secreted proteins important for biomineralization (Cui et al., 2015). Here we report the nucleotide-free and ATP-bound structures of ...
متن کامل