Fam20a-flox Mouse

Fam20a, Family with Sequence Similarity 20, Member A, is a pseudo-kinase in the secretory pathway. It binds to FAM20C, the Golgi casein kinase, and potentiates its function to phosphorylate secreted proteins crucial for biomineralization. FAM20A is essential for amelogenesis and maintaining pulp tissue homeostasis, preventing ectopic mineralization in soft tissues [1,2].

In a Sox2-Cre;Fam20afl/fl KO mouse model, mice developed an enamel phenotype resembling human amelogenesis imperfecta associated with FAM20A mutations, but had no apparent dentin defects. Secretory-stage ameloblasts were shorter, detached from the enamel matrix, lost polarity, and formed abnormal extracellular matrices. The expression of enamel matrix protein-encoding genes was reduced, while that of dentin matrix proteins remained unchanged. Also, Fam20a ablation led to a decrease in FAM20C protein level [2]. In another study with epithelial-specific Fam20a knockout in mice, it led to short root defects, with irregular breaks in the epithelial root sheath, initiation of the WNT signaling pathway, and decreased expression of the cell polarity-related transcription factor Cdc42. The osteoclast peak around the mandibular first molar was delayed, causing slower eruption pathway formation and delayed tooth eruption [3].

In conclusion, Fam20a is vital for amelogenesis, pulp tissue homeostasis, and tooth root development. The KO mouse models have revealed its role in preventing ectopic mineralization, and its importance in enamel and tooth root formation. These findings enhance our understanding of diseases like enamel renal syndrome, which is caused by FAM20A mutations [1,3,4,5].