Next-generation sequencing to dissect hereditary nephrotic syndrome in mice identifies a hypomorphic mutation in Lamb2 and models Pierson’s syndrome
Autor: | Karlee Silver, Thomas Mason, Christopher C. Goodnow, Shirine Chaudhry, Tiphaine Bouriez-Jones, Ian Roberts, Andrew J. Rimmer, Tertius A Hough, Tanya L. Crockford, Richard J. Cornall, Katherine R. Bull |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Mice
129 Strain Nephrotic Syndrome DNA Mutational Analysis Mutagenesis (molecular biology technique) Biology medicine.disease_cause DNA sequencing Pathology and Forensic Medicine Podocyte Mice Pupil Disorders congenital nephrosis medicine Animals Abnormalities Multiple Genetic Predisposition to Disease Eye Abnormalities Gene Genetic Association Studies Genetics Myasthenic Syndromes Congenital Mutation Glomerular basement membrane animal model High-Throughput Nucleotide Sequencing medicine.disease Phenotype Original Papers Mice Mutant Strains 3. Good health Pedigree kidney glomerulus Mice Inbred C57BL Disease Models Animal Proteinuria medicine.anatomical_structure Kidney Tubules glomerular basement membrane Ethylnitrosourea next-generation sequencing Laminin Nephrotic syndrome mutagenesis |
Zdroj: | The Journal of Pathology |
ISSN: | 1096-9896 0022-3417 |
Popis: | 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. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd |
Databáze: | OpenAIRE |
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