N-ethyl-N-nitrosourea-Induced Adaptor Protein 2 Sigma Subunit 1 (<i>Ap2s1</i>) Mutations Establish <i>Ap2s1</i> Loss-of-Function Mice.

ABSTRACT: The adaptor protein-2 sigma subunit (AP2σ), encoded by AP2S1, forms a heterotetrameric complex, with AP2α, AP2β, and AP2μ subunits, that is pivotal for clathrin-mediated endocytosis, and AP2σ loss-of-function mutations impair internalization of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor, and cause familial hypocalciuric hypercalcemia type-3 (FHH3). Mice with AP2σ mutations that would facilitate investigations of the in vivo role of AP2σ, are not available, and we therefore embarked on establishing such mice. We screened >10,000 mice treated with the mutagen N-ethyl-N-nitrosourea (ENU) for Ap2s1 mutations and identified 5 Ap2s1 variants, comprising 2 missense (Tyr20Asn and Ile123Asn) and 3 intronic base substitutions, one of which altered the inva

SUBMITTER: Gorvin CM 

PROVIDER: S-EPMC5824975 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature