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A spontaneous mutation in Srebf2 leads to cataracts and persistent skin wounds in the lens opacity 13 (lop13) mouse.

ABSTRACT: Lens opacity 13 (lop13) is a spontaneous, autosomal recessive mouse mutant that exhibits nuclear cataracts. Histological analysis revealed swollen lens fiber cells and the presence of bladder cells within the lens cortex, as well as morgagnian globules and liquefied material at the lens posterior. At 3 months of age, in addition to cataracts, lop13 mice also develop persistent skin wounds. Linkage analysis assigned the lop13 locus to a 1.1-Mb region on mouse Chr 15, encompassing 19 candidate genes. Sequence analysis identified a C3112T mutation in exon 18 of Sterol Regulatory Element Binding-Transcription Factor 2 (Srebf2) resulting in the R1038C substitution of a highly conserved arginine within the Srebf2 regulatory domain. Srebf2 belongs to a family of membrane-bound basic helix-loop-helix leucine zipper transcription factors that control the expression of genes involved in the biosynthesis and uptake of cholesterol and fatty acids. The lack of complementation observed in Srebf2 ( lop13/GT ) compound heterozygotes carrying the Srebf2 gene trapped allele (Srebf2 ( GT )) provides genetic evidence that the identified C3112T substitution in Srebf2 is responsible for the lop13 phenotype. Gas chromatography analysis identified lower levels of cholesterol in the lop13 brain, liver, and lens when compared to wild-type mice. These findings suggest that lop13 is a hypomorphic mutation in Srebf2. As such, the lop13 mouse presents an invaluable in vivo model for studying the contribution of Srebf2 and cholesterol to maintaining the homeostasis of the lens and skin.

SUBMITTER: Merath KM

PROVIDER: S-EPMC3251904 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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A spontaneous mutation in Srebf2 leads to cataracts and persistent skin wounds in the lens opacity 13 (lop13) mouse.

Merath Kate M KM Chang Bo B Dubielzig Richard R Jeannotte Richard R Sidjanin Duska J DJ

Mammalian genome : official journal of the International Mammalian Genome Society 20110821 11-12

Lens opacity 13 (lop13) is a spontaneous, autosomal recessive mouse mutant that exhibits nuclear cataracts. Histological analysis revealed swollen lens fiber cells and the presence of bladder cells within the lens cortex, as well as morgagnian globules and liquefied material at the lens posterior. At 3 months of age, in addition to cataracts, lop13 mice also develop persistent skin wounds. Linkage analysis assigned the lop13 locus to a 1.1-Mb region on mouse Chr 15, encompassing 19 candidate gen ...[more]

PMID: 21858719

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Project description:ObjectiveTo compare the efficacy and safety of the intraocular lens (IOL)-shell procedure versus conventional phacoemulsification for the surgical treatment of dense cataracts.MethodsEighty eyes with dense nuclear cataracts were enrolled in a prospective, randomized controlled study. Patients were assigned to two groups. In Group I, the IOL was traditionally implanted after all nuclear fragments were completely removed, and in Group II, the IOL was innovatively implanted in the bag before the last residual nuclear fragment was removed. This novel adjusted surgical procedure, named the "IOL-shell technique", features use of the IOL as a protective barrier rather than simply as a refractive alternative, and it is conceptually different from the traditional step-by-step procedure. Clinical examinations, including uncorrected visual acuity, central corneal thickness (CCT), temporal clear corneal incision thickness and corneal endothelial cell density, were carried out.ResultsThe inter-group difference in temporal corneal thickness was found to be of no statistical significance at any of the visits. Compared to eyes in Group I, those in Group II were shown to have significantly less corneal endothelial cell loss on both the 7th and 30th day following surgery. At 7 days after surgery, the mean corneal endothelial cell loss in Group II was 10.29%, compared to 14.37% in Group I (P<0.05). The mean endothelial cell loss measured on postoperative day 30 was 16.88% in Group II compared to 23.32% in Group I (P<0.05). On the 1st day after surgery, the mean CCT of eyes in Group II was significantly smaller compared to Group I (Group I vs. Group II: 19.42% vs. 13.50%, P<0.05).ConclusionsCompared to conventional phacoemulsification, the IOL-shell technique was shown to be a relatively safer procedure without compromised efficiency for dense cataracts, and it caused less corneal endothelial cell loss and milder postoperative corneal edema (Clinical Trials Identifier: NCT02138123).Trial registrationClinicalTrials.gov NCT02138123.

Project description:BackgroundThe eye is well known to be sensitive to clearly high doses (>2 Gy) of ionizing radiation. In recent years, however, cataracts have been observed in populations exposed to lower doses. Interventional cardiologists are repeatedly and acutely exposed to scattered ionizing radiation (X-rays) during the diagnostic and therapeutic procedures they perform. These "low" exposures may cause damage to the lens of the eye and induce early cataracts, known as radiation-induced cataracts. The O'CLOC study (Occupational Cataracts and Lens Opacities in interventional Cardiology) was designed to test the hypothesis that interventional cardiologists, compared with an unexposed reference group of non-interventional cardiologists, have an increased risk of cataracts.Method/designThe O'CLOC study is a cross-sectional study that will include a total of 300 cardiologists aged at least 40 years: one group of exposed interventional cardiologists and another of non-interventional cardiologists. The groups will be matched for age and sex. Individual information, including risk factors for cataracts (age, diabetes, myopia, etc.), will be collected during a telephone interview. A specific section of the questionnaire for the exposed group focuses on occupational history, including a description of the procedures (type, frequency, radiation protection tool) used. These data will be used to classify subjects into "exposure level" groups according to cumulative dose estimates. Eye examinations for all participants will be performed to detect cataracts, even in the early stages (lens opacities, according to LOCS III, the international standard classification). The analysis will provide an estimation of the cataract risk in interventional cardiology compared with the unexposed reference group, while taking other risk factors into account. An analysis comparing the risks according to level of exposure is also planned.DiscussionThis epidemiological study will provide further evidence about the potential risk of radiation-induced cataracts at low doses and contribute to cardiologists' awareness of the importance of radiation protection.Trial registrationNCT01061463.

Project description:PurposeCataract is the most prevalent cause of blindness in Nepal. Several epidemiologic studies have associated cataracts with use of biomass cookstoves. These studies, however, have had limitations, including potential control selection bias and limited adjustment for possible confounding. This study, in Pokhara City, in an area of Nepal where biomass cookstoves are widely used without direct venting of the smoke to the outdoors, focuses on preclinical measures of opacity while avoiding selection bias and taking into account comprehensive data on potential confounding factors.MethodsUsing a cross-sectional study design, severity of lenticular damage, judged on the LOCS (Lens Opacities Classification System) III scales, was investigated in women (n = 143), aged 20 to 65 years, without previously diagnosed cataract. Linear and logistic regression analyses were used to examine the relationships with stove type and length of use. Clinically significant cataract, used in the logistic regression models, was defined as a LOCS III score ≥2.ResultsUsing gas cookstoves as the reference group, logistic regression analysis for nuclear cataract showed evidence of relationships with stove type: for biomass stoves, the odds ratio was 2.58 (95% confidence interval, 1.22 to 5.46); and for kerosene stoves, the odds ratio was 5.18 (95% confidence interval, 0.88 to 30.38). Similar results were found for nuclear color (LOCS III score ≥2), but no association was found with cortical cataracts. Supporting a relationship between biomass stoves and nuclear cataract was a trend with years of exposure to biomass cookstoves (p = 0.01). Linear regression analyses did not show clear evidence of an association between lenticular damage and stove types. Biomass fuel used for heating was not associated with any form of opacity.ConclusionsThis study provides support for associations of biomass and kerosene cookstoves with nuclear opacity and change in nuclear color. The novel associations with kerosene cookstove use deserve further investigation.

Dataset Information

A spontaneous mutation in Srebf2 leads to cataracts and persistent skin wounds in the lens opacity 13 (lop13) mouse.

Publications

A spontaneous mutation in Srebf2 leads to cataracts and persistent skin wounds in the lens opacity 13 (lop13) mouse.

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