Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice

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 homozy...

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Main Authors:	Doray, Balraj, Govero, Jennifer, Kornfeld, Stuart
Format:	Online
Language:	English
Published:	Genetics Society of America 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025487/

id	pubmed-4025487
recordtype	oai_dc
spelling	pubmed-40254872014-05-30 Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice Doray, Balraj Govero, Jennifer Kornfeld, Stuart Investigations 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. Genetics Society of America 2014-03-17 /pmc/articles/PMC4025487/ /pubmed/24637350 http://dx.doi.org/10.1534/g3.114.010355 Text en Copyright © 2014 Doray et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Doray, Balraj Govero, Jennifer Kornfeld, Stuart
spellingShingle	Doray, Balraj Govero, Jennifer Kornfeld, Stuart Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice
author_facet	Doray, Balraj Govero, Jennifer Kornfeld, Stuart
author_sort	Doray, Balraj
title	Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice
title_short	Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice
title_full	Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice
title_fullStr	Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice
title_full_unstemmed	Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice
title_sort	impact of genetic background on neonatal lethality of gga2 gene-trap mice
description	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.
publisher	Genetics Society of America
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025487/
_version_	1612090545311580160

Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice

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