Academic Journal
A human amelotin transgenic mouse model with calcified deposits similar to those in dry age-related macular degeneration.
| Τίτλος: | A human amelotin transgenic mouse model with calcified deposits similar to those in dry age-related macular degeneration. |
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| Συγγραφείς: | Rajapakse D; Section on Molecular Structure and Functional Genomics, National Institutes of Health, National Eye Institute, Bethesda, MD, 20892, United States., Fan J; Section on Molecular Structure and Functional Genomics, National Institutes of Health, National Eye Institute, Bethesda, MD, 20892, United States., Daily D; Section on Molecular Structure and Functional Genomics, National Institutes of Health, National Eye Institute, Bethesda, MD, 20892, United States., Dong L; Genetic Engineering Core, National Institutes of Health, National Eye Institute, Bethesda, MD, 20892, United States., Peterson K; Section on Molecular Structure and Functional Genomics, National Institutes of Health, National Eye Institute, Bethesda, MD, 20892, United States., Fariss R; Biological Imaging Core, National Institutes of Health, National Eye Institute, Bethesda, MD, 20892, United States., Wistow G; Section on Molecular Structure and Functional Genomics, National Institutes of Health, National Eye Institute, Bethesda, MD, 20892, United States. Electronic address: wistowg@nih.gov. |
| Πηγή: | Experimental eye research [Exp Eye Res] 2026 Aug; Vol. 269, pp. 111068. Date of Electronic Publication: 2026 May 13. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Academic Press Country of Publication: England NLM ID: 0370707 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0007 (Electronic) Linking ISSN: 00144835 NLM ISO Abbreviation: Exp Eye Res Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Academic Press Original Publication: London. |
| Ιατρικοί όροι (MeSH): | Calcinosis*/metabolism , Calcinosis*/pathology , Calcinosis*/genetics , Retinal Pigment Epithelium*/metabolism , Retinal Pigment Epithelium*/pathology , Geographic Atrophy*/metabolism , Geographic Atrophy*/pathology , Geographic Atrophy*/genetics , Macular Degeneration*/metabolism , Macular Degeneration*/pathology , Disease Models, Animal*, Calcium Phosphates/metabolism ; Cholesterol/metabolism ; Animals ; Mice, Transgenic ; Mice ; Humans ; Mice, Inbred C57BL |
| Περίληψη: | Amelotin (AMTN), a protein involved in enamel formation, is induced in retinal pigment epithelial (RPE) in patients with dry age-related macular degeneration (AMD) and is associated with calcification in drusen. To examine the effects of constitutive expression of human AMTN in RPE we created a transgenic (TG) mouse model that expresses human AMTN specifically in the RPE using the regulatory components of the mouse Rpe65 gene. This led to several AMD-like abnormalities in RPE but did not produce calcified depositions. Reasoning that other aspects of cell stress or damage may be needed for calcification we tested moderate laser injury of the retina in young TG and WT mice. TG mice, but not WT, developed AMTN-dependent deposits containing AMTN, cholesterol, and calcium phosphate/HAP in the laser lesions, reminiscent of deposits seen in dry AMD drusen. While laser lesions in WT mice healed normally, those in TG mice progressed, obliterating adjacent photoreceptors and recruiting microglia. This shows that chronic expression of AMTN can induce pathologies in RPE and that when coupled with injury can form structures similar to calcified drusen. These deposits are associated with increased retinal damage and inflammation. The model presents a system to test possible therapeutic effects of inhibition or suppression of AMTN in RPE in vivo. (Published by Elsevier Ltd.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Grant Information: | Z01 EY000433 United States ImNIH Intramural NIH HHS |
| Contributed Indexing: | Keywords: Age-related macular degeneration; Amelotin; Calcium phosphate; Disease models; Drusen; Hydroxyapatite; Mouse models |
| Substance Nomenclature: | 0 (Calcium Phosphates) 97C5T2UQ7J (Cholesterol) |
| Entry Date(s): | Date Created: 20260514 Date Completed: 20260612 Latest Revision: 20260612 |
| Update Code: | 20260613 |
| PubMed Central ID: | PMC13209737 |
| DOI: | 10.1016/j.exer.2026.111068 |
| PMID: | 42134448 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1096-0007 |
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| DOI: | 10.1016/j.exer.2026.111068 |