Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice. Issue 5 (1st May 2014)

• Record Type: Journal Article
• Authors: Doray, Balraj; Govero, Jennifer; Kornfeld, Stuart
• Is Part Of: G3. Volume 4:Issue 5(2014)
• Page Start: 885
• Page End: 890
• Publication Date: 2014-05-01
• Subjects: GGA2 -- gene-trap -- hypomorphic allele -- neonatal lethality -- genetic background; Genetics -- Research -- Periodicals; Genomics -- Periodicals; Genetics; Genomics; Genes; Genetics -- Research; Genomics; Electronic journals; Periodical; Periodicals; Fulltext; Internet Resources; Periodicals; 572.8
• DOI: 10.1534/g3.114.010355
• Languages: English
• ISSNs: 2160-1836

Abstract

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.