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

ABSTRACT: The functional redundancy of the three mammalian Golgi-localized, ?-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.

SUBMITTER: Doray B

PROVIDER: S-EPMC4025487 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Doray Balraj B Govero Jennifer J Kornfeld Stuart S

G3 (Bethesda, Md.) 20140317 5

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). W ...[more]

PMID: 24637350

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

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

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