HSF4 Mutation p.Arg116His Found in Age-Related Cataracts and in Normal Populations Produces Childhood Lamellar Cataract in Transgenic Mice
| Autor: | Ankur M. Bhat, Yoshiko Nagaoka, Suraj P. Bhat, Meisheng Jiang, Zhe Jing, Rajendra K. Gangalum |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty genetic structures DNA Mutational Analysis Genetic Vectors Mice Transgenic Penetrance Biology Article Cataract Mice Heat Shock Transcription Factors Cataracts Internal medicine Gene Order Genetics medicine Animals Humans Child Transcription factor Genetics (clinical) Bacterial artificial chromosome Age Factors medicine.disease Phenotype eye diseases DNA-Binding Proteins Transgenesis Disease Models Animal Endocrinology Amino Acid Substitution Child Preschool Mutation Age-related cataract Transcription Factors |
| Zdroj: | Human Mutation. 35:1068-1071 |
| ISSN: | 1059-7794 |
| Popis: | The p.Arg116His mutation in the heat shock transcription factor-4 (HSF4) has been associated with age-related cataracts, but it is also seen in 2% of the normal population, indicating either reduced penetrance or that the normal subjects were not old enough to express the phenotype. Based on the proximity of p.Arg116His to two known mutations in the DNA-binding domain of HSF4, namely, p.Leu114Pro and p.Arg119Cys, which segregate with childhood lamellar cataract, we tested the possibility that this phenotype may have been missed by the ophthalmologist and/or that it did not spread to the visual axis so as to affect vision significantly. Here, we demonstrate via BAC (bacterial artificial chromosome) transgenesis that p.Arg116His recreates the childhood lamellar cataract in mice suggesting that incomplete penetrance associated with early cataracts may not be an absence but a limitation of the detection of the phenotype. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text