Histopathological characterisation of effects of the mouse Pax6Leca4 missense mutation on eye development
| Autor: | Kanna Ramaesh, Steven Williams, Thaya Ramaesh, Baljean Dhillon, Catriona Paul, John D. West |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Heterozygote endocrine system Pathology medicine.medical_specialty PAX6 Transcription Factor genetic structures Mutation Missense Biology Eye Microphthalmia Mice Cellular and Molecular Neuroscience Ciliary body Cornea Lens Crystalline medicine Animals Microphthalmos Paired Box Transcription Factors Missense mutation Eye Abnormalities Eye Proteins Corneal epithelium Homeodomain Proteins Homozygote medicine.disease eye diseases Sensory Systems Repressor Proteins Disease Models Animal Ophthalmology medicine.anatomical_structure Persistent hyperplastic primary vitreous Mice Inbred CBA Eye development Female sense organs PAX6 |
| Zdroj: | Experimental Eye Research. 89:263-273 |
| ISSN: | 0014-4835 |
| DOI: | 10.1016/j.exer.2009.03.016 |
| Popis: | Mutations in PAX6/Pax6 lead to a variety of ocular anomalies in humans and mice. The aim of the study was to characterise the ocular abnormalities caused by the missense Pax6(Leca4) mutation and compare them to published observations on Pax6 alleles that are functionally equivalent to Pax6(-) null alleles (such as Pax6(Sey) and Pax6(Sey-Neu)) and human inherited eye diseases. Ocular features of homozygous Pax6(Leca4)(/Leca4) and heterozygous Pax6(Leca4)(/+) embryos at E12.5-E18.5, heterozygous Pax6(Leca4)(/+) young mice at P18 and heterozygous Pax6(Leca4)(/+) adults at 12 weeks were analysed histologically with their wild-type Pax6(+/+) littermates. Homozygous Pax6(Leca4)(/Leca4) fetuses died perinatally with no eyes although an optic cup rudiment with pigmented cells developed. Pax6(Leca4)(/+) mice were microphthalmic and a range of other severe ocular phenotypes affected both the anterior and the posterior segments. In contrast to Pax6(+/-), the Pax6(Leca4)(/+) eyes had no goblet cells in the corneal epithelium, the iris was not hypoplastic and there was no lens-corneal epithelial plug. However, microphthalmia was more severe, corneal vascularisation occurred earlier (during fetal stages), pigmented cells were present in the vitreous and corneal stroma and the ciliary body was malformed or abnormal. These results show that, although Pax6(Leca4)(/+) lacked some eye abnormalities commonly seen in Pax6(Sey)(/+) and Pax6(Sey-Neu)(/+) eyes, in most respects their eyes were more severely affected. These differences probably reflect both differences between the Pax6(Leca4) and the Pax6(Sey-Neu) mutations and differences in modifier gene expression in different genetic backgrounds. The presence of pigmented cells in the cornea is a novel observation. Some Pax6(Leca4)(/+) ocular abnormalities were similar to those present in human Peters' anomaly and persistent hyperplastic primary vitreous (PHPV) so Pax6(Leca4)(/+) mice provide a useful model for some inherited eye diseases. |
| Databáze: | OpenAIRE |
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