Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uveal melanoma (UM) is uncommon among wild type mice. Efforts to develop transgenic mice to study this disease have resulted in pigmented tumors derived from the retinal pigment epithelium (RPE) or mixed tumors of RPE and UM complicating the study of UM specifically. Reported here are two early stage intraocular amelanotic melanomas discovered in 2 Tyr-HRAS+ Ink4a/Arf heterozygous (1 normal CKDN2A allele) transgenic FVB/n mice. These tumors were morphologically and immunohistochemically similar to spontaneous UM recently reported in the Ink4a/Arf homozygous (CKDN2A knockout) parent strain. The tumors originated in the posterior uveal tract. The neoplasms were comprised of bundles of spindle-shaped melanocytes admixed with some epithelioid cells. Tumors were immunohistochemically positive for neuron-specific enolase, S-100, pan-ras, but negative for cytokeratin and Melan-A. The development of early lenticular opacity and bilateral cataracts is a consistent phenotype of transgenic mice in which the retinoblastoma signaling pathway has been disrupted. Lenticular opacity and cataracts are rarely observed clinically in Tyr-HRAS+ Ink4a/Arf heterozygotes, rendering this strain suitable for ophthalmoscopy. Consequently, Tyr-HRAS+ Ink4a/Arf heterozygotes provide practical advantages, compared to the cataract-prone CKDN2A knockout strains, for real-time ophthalomoscopic detection and monitoring of UM while developing chemotherapeutic regimens and other research to understand the biology of UM.
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PMID:Two cases of uveal amelanotic melanoma in transgenic Tyr-HRAS+ Ink4a/Arf heterozygous mice. 1798 14

Bin3 encodes an evolutionarily conserved and ubiquitously expressed member of the BAR superfamily of curved membrane and GTPase-binding proteins, which includes the BAR, PCH/F-BAR, and I-BAR adapter proteins implicated in signal transduction and vesicular trafficking. In humans, Bin3 maps to chromosome 8p21.3, a region widely implicated in cancer suppression that is often deleted in non-Hodgkin's lymphomas and various epithelial tumors. Yeast studies have suggested roles for this gene in filamentous actin (F-actin) organization and cell division but its physiologic functions in mammals have not been investigated. Here we report that homozygous inactivation of Bin3 in the mouse causes cataracts and an increased susceptibility to lymphomas during aging. The cataract phenotype was marked by multiple morphologic defects in lens fibers, including the development of vacuoles in cortical fibers and a near total loss of F-actin in lens fiber cells but not epithelial cells. Through 1 year of age, no other phenotypes were apparent; however, by 18 months of age, Bin3(-/-) mice exhibited a significantly increased incidence of lymphoma. Bin3 loss did not affect normal cell proliferation, F-actin organization, or susceptibility to oncogenic transformation. In contrast, it increased the proliferation and invasive motility of cells transformed by SV40 large T antigen plus activated ras. Our findings establish functions for Bin3 in lens development and cancer suppression during aging. Further, they define Bin3 as a candidate for an unidentified tumor suppressor that exists at the human chromosome 8p21.3 locus.
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PMID:Bin3 deletion causes cataracts and increased susceptibility to lymphoma during aging. 1833 47