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


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
Laboratory mice
Electron Microscopy

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Lipidomics & Rhinovirus Infection

Lipidomics can be used to examine the lipid species involved with pathogenic conditions, such as viral associated inflammation. Discovered the latest research on Lipidomics & Rhinovirus Infection.

Alzheimer's Disease: MS4A

Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Torsion Dystonia

Torsion dystonia is a movement disorder characterized by loss of control of voluntary movements appearing as sustained muscle contractions and/or abnormal postures. Here is the latest research.

Generating Insulin-Secreting Cells

Reprogramming cells or using induced pluripotent stem cells to generate insulin-secreting cells has significant therapeutic implications for diabetics. Here is the latest research on generation of insulin-secreting cells.

Central Pontine Myelinolysis

Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.

Epigenome Editing

Epigenome editing is the directed modification of epigenetic marks on chromatin at specified loci. This tool has many applications in research as well as in the clinic. Find the latest research on epigenome editing here.

Related Papers

Investigative Ophthalmology & Visual Science
Chun-Hong XiaXiaohua Gong
The European Journal of Neuroscience
Ronja BahadoriStephan C F Neuhauss
© 2021 Meta ULC. All rights reserved