title: Impact of genetic background on neonatal lethality of Gga2 gene-trap mice.
abstract: The functional redundancy of the three mammalian Golgi-localized, γ-ear-containing, ADP-ribosylation factor-binding proteins (GGAs) was addressed in a previous study. Using insertional mutagenesis, we found that Gga1 or Gga3 homozygous knockout mice were for the most part normal, whereas mice homozygous for two different Gga2 gene-trap alleles exhibited either embryonic or neonatal lethality in the C57BL/6 background, depending on the source of the vector utilized (Byg vs. Tigm, respectively). We now show that the Byg strain harbors a disrupted Gga2 allele that is hypomorphic, indicating that the Byg lethality is attributable to a mechanism independent of GGA2. This is in contrast to the Tigm Gga2 allele, which is a true knockout and establishes a role for GGA2 during the neonatal period. Placement of the Tigm Gga2 allele into the C57BL6/Ola129Sv mixed background results in a lower incidence of neonatal lethality, showing the importance of genetic background in determining the requirement for GGA2 during this period. The Gga2(-/-) mice that survive have reduced body weight at birth and this runted phenotype is maintained through adulthood.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Balraj
authors.initials: B
authors.lastname: Doray
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Govero
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110 skornfel@dom.wustl.edu.
authors.forename: Stuart
authors.initials: S
authors.lastname: Kornfeld
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000483:Alleles; D000818:Animals; D005260:Female; D005804:Genes, Lethal; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C572440:GGA2 protein, mouse
keywords: GGA2; gene-trap; genetic background; hypomorphic allele; neonatal lethality