Impact of genetic background on neonatal lethality of Gga2 gene-trap mice

Balraj Doray, Jennifer Govero, Stuart Kornfeld

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The functional redundancy of the three mammalian Golgi-localized, α-ear-containing, ADPribosylation 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.

Original languageEnglish
Pages (from-to)885-890
Number of pages6
JournalG3: Genes, Genomes, Genetics
Volume4
Issue number5
DOIs
StatePublished - 2014

Keywords

  • GGA2
  • Gene-trap hypomorphic allele
  • Genetic background
  • Neonatal lethality

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