Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The study of mutations causing the steroid-resistant nephrotic syndrome in children has greatly advanced our understanding of the kidney filtration barrier. In particular, these genetic variants have illuminated the roles of the podocyte, glomerular basement membrane and endothelial cell in glomerular filtration. However, in a significant number of familial and early onset cases, an underlying mutation cannot be identified, indicating that there are likely to be multiple unknown genes with roles in glomerular permeability. We now show how the combination of N-ethyl-N-nitrosourea mutagenesis and next-generation sequencing could be used to identify the range of mutations affecting these pathways. Using this approach, we isolated a novel mouse strain with a viable nephrotic phenotype and used whole-genome sequencing to isolate a causative hypomorphic mutation in Lamb2. This discovery generated a model for one part of the spectrum of human Pierson's syndrome and provides a powerful proof of principle for accelerating gene discovery and improving our understanding of inherited forms of renal disease.

Original publication

DOI

10.1002/path.4308

Type

Journal article

Journal

The Journal of pathology

Publication Date

05/2014

Volume

233

Pages

18 - 26

Addresses

Nuffield Department of Medicine and Wellcome Trust Centre for Human Genetics, Oxford University, UK.

Keywords

Kidney Tubules, Animals, Mice, Inbred C57BL, Mice, Mice, Mutant Strains, Pupil Disorders, Eye Abnormalities, Nephrotic Syndrome, Proteinuria, Abnormalities, Multiple, Disease Models, Animal, Genetic Predisposition to Disease, Ethylnitrosourea, Laminin, Pedigree, DNA Mutational Analysis, Phenotype, Mutation, Genetic Association Studies, Mice, 129 Strain, High-Throughput Nucleotide Sequencing