Predicting human disease mutations and identifying drug targets from mouse gene knockout phenotyping campaigns.
Knockout mice
Mouse models
Phenomics
Phenotyping
Translational medicine
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
07 05 2019
07 05 2019
Historique:
entrez:
9
5
2019
pubmed:
9
5
2019
medline:
6
2
2020
Statut:
epublish
Résumé
Two large-scale mouse gene knockout phenotyping campaigns have provided extensive data on the functions of thousands of mammalian genes. The ongoing International Mouse Phenotyping Consortium (IMPC), with the goal of examining all ∼20,000 mouse genes, has examined 5115 genes since 2011, and phenotypic data from several analyses are available on the IMPC website (www.mousephenotype.org). Mutant mice having at least one human genetic disease-associated phenotype are available for 185 IMPC genes. Lexicon Pharmaceuticals' Genome5000™ campaign performed similar analyses between 2000 and the end of 2008 focusing on the druggable genome, including enzymes, receptors, transporters, channels and secreted proteins. Mutants (4654 genes, with 3762 viable adult homozygous lines) with therapeutically interesting phenotypes were studied extensively. Importantly, phenotypes for 29 Lexicon mouse gene knockouts were published prior to observations of similar phenotypes resulting from homologous mutations in human genetic disorders. Knockout mouse phenotypes for an additional 30 genes mimicked previously published human genetic disorders. Several of these models have helped develop effective treatments for human diseases. For example, studying
Identifiants
pubmed: 31064765
pii: 12/5/dmm038224
doi: 10.1242/dmm.038224
pmc: PMC6550044
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2019. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsD.R.P. is currently employed at Lexicon Pharmaceuticals and has stock shares and stock options. R.B. and P.V. were previously employed at Lexicon Pharmaceuticals. R.B. owns Lexicon stock shares. P.V. has no financial interests.
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