Early embryonic death of mice deficient in gamma-adaptin

Intracellular protein transport and sorting by vesicles in the secretory an d endocytic pathways requires the formation of a protein coat on the membra ne. The heterotetrameric adaptor protein complex 1 (AP-1) promotes the form ation of clathrin-coated vesicles at the trans-Golgi network. AP-1 interact s with various sorting signals in the cytoplasmic tails of cargo molecules, thus indicating a function in protein sorting. We generated mutants of the gamma-adaptin subunit of AP-1 in mice to investigate its role in post-Golg i vesicle transport and sorting processes. gamma-Adaptin-deficient embryos develop until day 3.5 post coitus and die during the prenidation period, re vealing that AP-1 is essential for viability. In heterozygous mice the amou nt of AP-1 complexes is reduced to half of controls. Free beta 1- or mu 1 c hains were not detectable, indicating that they are unstable unless they ar e part of AP-1 complexes. Heterozygous mice weigh less then their wild-type littermates and show impaired T cell development.