{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ACP4 is an enamel‐specific protein that plays a critical role during amelogenesis, particularly in the secretory stage of ameloblast differentiation and enamel matrix formation. Mutations in ACP4 disturb normal enamel development, leading to hypoplastic amelogenesis imperfecta, as demonstrated in canine models where a frameshift mutation in ACP4 was associated with abnormally thin, yet mineralized, enamel."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In an evolutionary context, molecular evolutionary analyses of enamel‐related genes have revealed that inactivating mutations in ACP4 (along with other enamel genes such as KLK4 and MMP20) are shared among certain baleen whale lineages, supporting a model whereby early loss of enamel preceded subsequent dentin/tooth loss. This finding underscores the importance of ACP4 in enamel biogenesis and highlights that its disruption is a major determinant of enamel deficiency across diverse mammalian lineages."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marjo K Hytönen, Meharji Arumilli, Eva Sarkiala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Canine models of human amelogenesis imperfecta: identification of novel recessive ENAM and ACP4 variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-019-01997-8"}], "href": "https://doi.org/10.1007/s00439-019-01997-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30877375"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30877375"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jason G Randall, John Gatesy, Mark S Springer "}, {"type": "b", "children": [{"type": "t", "text": "Molecular evolutionary analyses of tooth genes support sequential loss of enamel and teeth in baleen whales (Mysticeti)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Phylogenet Evol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ympev.2022.107463"}], "href": "https://doi.org/10.1016/j.ympev.2022.107463"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35358696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35358696"}]}]}]}