Evolutionary Story of Mammalian-specific Amelogenin Exons 4, “4b”, 8, and 9

Sire, Jean‐Yves; Huang, Yue; Li, W.; Delgado, Sidney; Goldberg, Michel; DenBesten, Pamela

doi:10.1177/0022034511423399

Cited by 11 publications

(21 citation statements)

References 25 publications

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“…The 6 affected persons had this sequence variation, and none of the 7 unaffected persons had it. This nucleotide change was well conserved in all species except for the opossum (Sire et al, 2012). Further sequencing of the other AI-related genes did not identify any disease-causing mutations.…”

Section: Identification Of a Silent Mutation In The Amelx Genementioning

confidence: 88%

Alteration of Conserved Alternative Splicing in AMELX Causes Enamel Defects

et al. 2014

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Tooth enamel is the most highly mineralized tissue in vertebrates. Enamel crystal formation and elongation should be well controlled to achieve an exceptional hardness and a compact microstructure. Enamel matrix calcification occurs with several matrix proteins, such as amelogenin, enamelin, and ameloblastin. Among them, amelogenin is the most abundant enamel matrix protein, and multiple isoforms resulting from extensive but wellconserved alternative splicing and postsecretional processing have been identified. In this report, we recruited a family with a unique enamel defect and identified a silent mutation in exon 4 of the AMELX gene. We show that the mutation caused the inclusion of exon 4, which is almost always skipped, in the mRNA transcript. We further show, by generating and characterizing a transgenic animal model, that the alteration of the ratio and quantity of the developmentally conserved alternative splicing repertoire of AMELX caused defects in enamel matrix mineralization.

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Section: Identification Of a Silent Mutation In The Amelx Genementioning

confidence: 88%

Alteration of Conserved Alternative Splicing in AMELX Causes Enamel Defects

et al. 2014

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“…Further studies of amelogenin in lower chordates are necessary to better understand the evolution of these exons. Another novel exon found between so-called exon 5 and 6 in a reptile, Ctenosaura similis 20) , and in mammals, newly exon 4b and 8 in AMELX have found as a result of duplication of so-called exon 4 and 5 21) .…”

Section: Discussionmentioning

confidence: 99%

Amelogenin in Frog Species, Xenopus tropicalis: A Gene Evolutionary Approach

Ando

Inage

Oida

2013

J. Hard Tissue Biology.

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The structure and function of the amelogenin gene on a tooth germs in the frog Xenopus tropicalis, were examined. Using PCR, we observed an intensive band of amelogenin in maxillas with teeth but not in the toothless mandibles, and in situ hybridization revealed the restricted expression of amelogenin only in secreting ameloblasts in a tooth germs. Sequence analyses indicated that two types of amelogenin mRNA were alternatively spliced and derived from a single gene. They are referred to here as amelogenin mRNA-A and -B. In unique 5'-UTR, mRNA-A has a long exon 1, which is much longer than the same exon in other animals' amelogenin, and both mRNA-A and -B possesses new exons, referred to here as exon 2a and 2b. The following protein coding region was divided into five exons, as in the case of another frog, Xenopus laevis, whose amelogenin sequence was closest to X. tropicalis, and the amelogenin of X. tropicalis may play a role in enamel formation, as in other animals. A pair of amelogenin mRNAs of X. tropicalis have the most primitive sequence among known mRNAs and, in particular, the extremely long exon 1, and the newly found exons 2a and 2b , may be key in exploring the archetype of amelogenin mRNA.

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“…Amelogenin exon4 is present in the amelogenin gene of many species (Sire et al 2012), and amelogenin proteins that contain exon4-encoded proteins have been reported in mouse (Simmer 1994) and porcine (Yamakoshi 2011) enamel matrix. Messenger RNAs (mRNAs) containing exon4 have been amplified from human (Salido et al 1992), mouse (Hu et al 1997), and rat (Li et al 1995) enamel organs.…”

Section: Introductionmentioning

confidence: 99%

Exon4 Amelogenin Transcripts in Enamel Biomineralization

et al. 2015

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Amelogenins are proteins formed by alternative splicing of the amelogenin gene, and are essential for tooth enamel formation. However, the unique functions of various alternatively spliced amelogenins in enamel formation are not well understood. In this study, we determined the spatiotemporal location of amelogenins derived from transcripts containing exon4 (AMG+4) in the enamel matrix, and the relative binding of recombinant AMG+4 to hydroxyapatite (HAP). Immunohistochemistry and mass spectrometry analyses showed that AMG+4 proteins were secreted into the enamel matrix at the early maturation stage. A stage-specific increase in the synthesis of AMG+4 was further supported by our observation that in mice overexpressing leucine-rich amelogenin peptide (TgLRAP), in which ameloblasts differentiate earlier, AMG+4 transcripts were also upregulated earlier. In vitro binding studies, supported by in silico modeling of protein binding to calcium and phosphate, showed that more recombinant AMG+4 bound to hydroxyapatite (HAP) as compared with recombinant AMG-4. The temporal and spatial localization of amelogenins containing exon4 peptide, and their functional differences in HAP binding, suggests that the unique properties of amelogenins containing exon4 cause a specific enhancement of biomineralization related to stabilization of early-formed HAP at the maturation stage.

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Evolutionary Story of Mammalian-specific Amelogenin Exons 4, “4b”, 8, and 9

Cited by 11 publications

References 25 publications

Alteration of Conserved Alternative Splicing in AMELX Causes Enamel Defects

Alteration of Conserved Alternative Splicing in AMELX Causes Enamel Defects

Amelogenin in Frog Species, Xenopus tropicalis: A Gene Evolutionary Approach

Exon4 Amelogenin Transcripts in Enamel Biomineralization

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