DOI: 10.1101/513846Jan 7, 2019Paper

Missense Mutations in the Human Nanophthalmos Gene TMEM98 Cause Retinal Defects in the Mouse

BioRxiv : the Preprint Server for Biology
Sally H CrossIan J. Jackson

Abstract

PURPOSE We previously found a dominant mutation, Rwhs , causing white spots on the retina accompanied by retinal folds. Here we identify the mutant gene to be Tmem98. In humans, mutations in the orthologous gene cause nanophthalmos. We modelled these mutations in mice and characterised the mutant eye phenotypes of these and Rwhs . METHODS The Rwhs mutation was identified to be a missense mutation in Tmem98 by genetic mapping and sequencing. The human TMEM98 nanophthalmos missense mutations were made in the mouse gene by CRISPR-Cas9. Eyes were examined by indirect ophthalmoscopy and the retinas imaged using a retinal camera. Electroretinography was used to study retinal function. Histology, immunohistochemistry and electron microscopy techniques were used to study adult eyes. RESULTS An I135T mutation of Tmem98 causes the dominant Rwhs phenotype and is perinatally lethal when homozygous. Two dominant missense mutations of TMEM98 , A193P and H196P are associated with human nanophthalmos. In the mouse these mutations cause recessive retinal defects similar to the Rwhs phenotype, either alone or in combination with each other, but do not cause nanophthalmos. The retinal folds did not affect retinal function as assessed by electro...Continue Reading

Related Concepts

Chromosome Mapping
Diagnostic Imaging
Electroretinography
Eye
Immunohistochemistry
Macrophage
Laboratory mice
Electron Microscopy
Ophthalmoscopy
Retina

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