title: Maternal enzyme masks the phenotype of mouse embryos lacking dihydrolipoamide dehydrogenase.
abstract: During early embryogenesis, the phenotype reflecting the embryonic genotype emerges only as maternal proteins are replaced by embryonically encoded forms, a process known as the maternal-to-embryonic transition (MET). Little is understood about MET for most proteins. This study investigates how complete deficiency of the murine dihydrolipoamide dehydrogenase gene (Dld), a gene that encodes an enzyme of mitochondrial energy metabolism, affects the phenotype of the early embryo and how the MET of the DLD protein affects the phenotype. Dld-deficient (-/-) embryos were found to develop similarly to wild-type (+/+) or heterozygous (+/-) embryos throughout the preimplantation period. These three genotypic classes also have comparable rates of glucose uptake (4.9-5.0 pmoles/embryo/h) and lactate production (0.97-1.0 pmoles/embryo/h). Dld-deficient embryos at the end of the preimplantation stage have 44% of DLD enzyme present in oocytes, a proportion similar to that found in +/+ or +/- embryos. This study demonstrates that Dld-deficient preimplantation embryos are phenotypically normal, as the MET for the DLD enzyme is only partially complete by the end of the preimplantation period. These findings have implications for phenotype- or enzyme-based approaches to identify mutations in Dld and other genes that encode proteins with similar MET kinetic profiles.
authors: Department of Obstetrics and Gynecology, University of Michigan School of Medicine, 1150 W. Medical Center Dr., 6422 Med Sci I, Ann Arbor, MI 48109-0617, USA. mtjohn@med.umich.edu
authors: Mark
authors: M
authors: Johnson
authors: Pa
authors: P
authors: Vang
authors: Jessica
authors: J
authors: Filipovits
authors: David
authors: D
authors: Gardner
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D008058:Dihydrolipoamide Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000201:enzymology; D047108:Embryonic Development; D004734:Energy Metabolism; D005260:Female; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D008058:Dihydrolipoamide Dehydrogenase