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Amelogenin (AMELX) and matrix metalloproteinase-20 (MMP20) are essential for proper enamel development. Amelx and Mmp20 mutations cause amelogenesis imperfecta. MMP20, a protease secreted by ameloblasts, is responsible for processing enamel proteins, including AMELX, during the secretory stage of enamel formation. Of at least 16 different amelogenin splice products, the most abundant isoform found in murine ameloblasts and developing enamel is the M180 protein. To understand the role of MMP20 processing of M180 AMELX, we generated AmelxKO/Mmp20KO (DKO) mice with an amelogenin (M180Tg) transgene. We analyzed the enamel phenotype by SEM to determine enamel structure and thickness, µCT, and by nanoindentation to quantify enamel mechanical properties. M180Tg/DKO mouse enamel had 37% of the hardness of M180Tg/AmelxKO teeth and demonstrated a complete lack of normal prismatic architecture. Although molar enamel of M180Tg/AmelxKO mice was thinner than WT, it had similar mechanical properties and decussating enamel prisms, which were abolished by the loss of MMP20 in the M180Tg/DKO mice. Retention of the C-terminus or complete lack of this domain is unable to rescue amelogenin null enamel. We conclude that among amelogenins, M180 alone is sufficient for normal enamel mechanical properties and prism patterns, but that additional amelogenin splice products are required to restore enamel thickness.

Doppler observations from Keck Observatory have revealed a triple-planet system orbiting the nearby K4V star, HIP 57274. The inner planet, HIP 57274b, is a super-Earth with Msin i = 11.6 M ⊕ (0.036M Jup), an orbital period of 8.135 0.004 days, and slightly eccentric orbit e = 0.19 0.1. We calculate a transit probability of 6.5% for the inner planet. The second planet has Msin i = 0.4M Jup with an orbital period of 32.0 0.02 days in a nearly circular orbit (e = 0.05 0.03). The third planet has Msin i = 0.53M Jup with an orbital period of 432 8 days (1.18 years) and an eccentricity e = 0.23 0.03. This discovery adds to the number of super-Earth mass planets with M sin i < 12 M ⊕ that have been detected with Doppler surveys. We find that 56% 18% of super-Earths are members of multi-planet systems. This is certainly a lower limit because of observational detectability limits, yet significantly higher than the fraction of Jupiter mass exoplanets, 20% 8%, that are members of Doppler-detected, multi-planet systems.

The abundant amelogenin proteins are responsible for generating proper enamel thickness and structure, and most amelogenins include a conserved hydrophilic C-terminus. To evaluate the importance of the C-terminus, we generated transgenic mice that express an amelogenin lacking the C-terminal 13 amino acids (CTRNC). MicroCT analysis of TgCTRNC29 teeth (low transgene number) indicated that molar enamel density was similar to that of wild-type mice, but TgCTRNC18 molar enamel (high transgene number) was deficient, indicating that extra transgene copies were associated with a more severe phenotype. When amelogenin-null (KO) and TgCTRNC transgenic mice were mated, density and volume of molar enamel from TgCTRNCKO offspring were not different from those of KO mice, indicating that neither TgCTRNC18 nor TgCTRNC29 rescued enamel’s physical characteristics. Because transgenic full-length amelogenin partially rescues both density and volume of KO molar enamel, it was concluded that the amelogenin C-terminus is essential for proper enamel density, volume, and organization.

FAM83H gene mutations are associated with autosomal-dominant hypocalcified amelogenesis imperfecta (ADHCAI), which is typically characterized by enamel having normal thickness and a markedly decreased mineral content. This study tested the hypothesis that there are phenotype and genotype associations in families with FAM83H-associated ADHCAI. Seven families segregating ADHCAI (147 individuals) were evaluated. Phenotyping included clinical, radiographic, histological, and biochemical studies, and genotyping was by mutational analysis. Multiple novel FAM83H mutations were identified, including two 2-bp-deletion mutations, the first non-nonsense mutations identified. Craniofacial deviation from normal was more prevalent in the affected individuals. Affected individuals having truncating FAMH3H mutations of 677 or fewer amino acids presented a generalized ADHCAI phenotype, while those having mutations capable of producing a protein of at least 694 amino acids had a unique and previously unreported phenotype affecting primarily the cervical enamel. This investigation shows that unique phenotypes are associated with specific FAM83H mutations.

Odontogenic lesions are rare, but can be associated with significant morbidity. While their molecular determinants are unknown, they likely express many genes common to normal odontogenesis. This study evaluated the histology and mRNA expression of an unusual odontogenic lesion in a patient with a confirmed history of tricho-dento-osseous syndrome. Methods: Decalcified, frozen 8 µm sections of the lesion were cut and mounted on glass slides and stained with hematoxylin/eosin for analysis. The expression of multiple genes associated with normal odontogenesis and related pathologies were evaluated by RT-PCR, where possible in samples of the hard and soft tissue components of the lesion. Results: Histological examination showed the lesion had large areas of irregular, dentine-like material, enamel matrix, areas of woven immature bone and multiple fully mineralised tooth crowns. Although most of the gene transcripts were amplified from both samples, some, including DLX3/7 and Collagen I demonstrated differential expression. Conclusions: This study shows the gene expression profile of aberrant odontogenesis with associated odontoma formation is similar to that of normal tooth and the genes expressed in other odontogenic lesions. While the role of altered gene expression in the development of such lesions has previously been postulated from transgenic models, this is the only report of an odontogenic lesion in a patient with TDO, and begins to elucidate possible gene interactions key to its development.