title: Analysis of Gga null mice demonstrates a non-redundant role for mammalian GGA2 during development.
abstract: Numerous studies using cultured mammalian cells have shown that the three GGAs (Golgi-localized, gamma-ear containing, ADP-ribosylation factor- binding proteins) function in the transport of cargo proteins between the trans- Golgi network and endosomes. However, the in vivo role(s) of these adaptor proteins and their possible functional redundancy has not been analyzed. In this study, the genes encoding GGAs1-3 were disrupted in mice by insertional mutagenesis. Loss of GGA1 or GGA3 alone was well tolerated whereas the absence of GGA2 resulted in embryonic or neonatal lethality, depending on the genetic background of the mice. Thus, GGA2 mediates a vital function that cannot be compensated for by GGA1and/or GGA3. The combined loss of GGA1 and GGA3 also resulted in a high incidence of neonatal mortality but in this case the expression level of GGA2 may be inadequate to compensate for the loss of the other two GGAs. We conclude that the three mammalian GGAs are essential proteins that are not fully redundant.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Govero
authors.forename: Balraj
authors.initials: B
authors.lastname: Doray
authors.forename: Hongdong
authors.initials: H
authors.lastname: Bai
authors.forename: Stuart
authors.initials: S
authors.lastname: Kornfeld
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005260:Female; D048788:Growth and Development / Q000235:genetics*; D006801:Humans; D008297:Male; D008322:Mammals / Q000196:embryology / Q000235:genetics / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family / Q000502:physiology; D013379:Substrate Specificity / Q000235:genetics
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C407306:GGA adaptor proteins; C405944:GGA2 protein, human; C572440:GGA2 protein, mouse