Abstract
Adaptor protein (AP) complexes function in the intracellular sorting and vesicular transport of membrane proteins. The clathrin-associated AP-1 complex functions at the trans-Golgi network and endosomes, and some forms of this complex are thought to mediate the sorting of proteins in plasma membranes of polarized epithelial cells. A null mutation of the mouse Ap1g1 gene, which encodes the gamma-1 subunit of the AP-1 complex, causes embryonic lethality when homozygous, indicating its critical importance in early development but precluding studies of its possible roles during later stages. Here, we describe our analyses of a new spontaneous mutation of Ap1g1 named “figure eight” (symbol fgt) and show that it is an in-frame deletion of 6 bp, which results in the elimination of two amino acids of the encoded protein. In contrast to Ap1g1 −/− null mice, mice homozygous for the recessive fgt mutation are viable with adult survival similar to controls. Although Ap1g1 is ubiquitously expressed, the phenotype of Ap1g1 fgt mutant mice is primarily restricted to abnormalities in sensory epithelial cells of the inner ear, pigmented epithelial cells of the retina, follicular epithelial cells of the thyroid gland, and the germinal epithelium of the testis, suggesting that impaired AP-1 sorting and targeting of membrane proteins in these polarized cells may underlie the observed pathologies. Ap1g1 fgt mutant mice provide a new animal model to study the in vivo roles of gamma-1 adaptin and the AP-1 complex throughout development and to investigate factors that underlie its associated phenotypic abnormalities.
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Acknowledgments
We thank Sandra Gray for mouse colony management and generation of linkage cross mice, Chantal Longo-Guess and Cong Tian for ABR threshold measurements, Norm Hawes for eye examinations, Mary Ann Handel for help interpreting testes pathology, and Jane Farley for CASA analysis. This research was supported by US National Institutes of Health (NIH) Grants DC004301 (KRJ) and EY019943 (BC). The Jackson Laboratory institutional shared services are supported in part by NIH National Cancer Institute Support Grant CA34196.
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Johnson, K.R., Gagnon, L.H. & Chang, B. A hypomorphic mutation of the gamma-1 adaptin gene (Ap1g1) causes inner ear, retina, thyroid, and testes abnormalities in mice. Mamm Genome 27, 200–212 (2016). https://doi.org/10.1007/s00335-016-9632-0
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DOI: https://doi.org/10.1007/s00335-016-9632-0