title: Targeted disruption of the mouse phosphomannomutase 2 gene causes early embryonic lethality.
abstract: Mutations in the cytosolic enzyme phosphomannomutase 2 (PMM2), which catalyzes the conversion of mannose-6-phosphate to mannose-1-phosphate, cause the most common form of congenital disorders of glycosylation, termed CDG-Ia. It is an inherited multisystemic disease with severe neurological impairment. To study the pathophysiology of CDG-Ia and to investigate possible therapeutic approaches, we generated a mouse model for CDG-Ia by targeted disruption of the Pmm2 gene. Heterozygous mutant mice appeared normal in development, gross anatomy, and fertility. In contrast, embryos homozygous for the Pmm2-null allele were recovered in embryonic development at days 2.5 to 3.5. These results indicate that Pmm2 is essential for early development of mice. Mating experiments of heterozygous mice with wild-type mice could further show that transmission of the female Pmm2-null allele is impaired.
authors.affiliation: Universitaetskinderklinik Heidelberg, Abteilung I, Friedrich Karls Universitaet Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany. Christian.Thiel@med.uni-heidelberg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Thiel
authors.forename: Torben
authors.initials: T
authors.lastname: Lübke
authors.forename: Gert
authors.initials: G
authors.lastname: Matthijs
authors.forename: Kurt
authors.initials: K
authors.lastname: von Figura
authors.forename: Christian
authors.initials: C
authors.lastname: Körner
mesh_terms: D000818:Animals; D002239:Carbohydrate Metabolism, Inborn Errors / Q000235:genetics*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000502:physiology*; D005260:Female; D018390:Gene Targeting; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D016366:Open Reading Frames; D010375:Pedigree; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D007527:Isoenzymes; D017875:Phosphotransferases (Phosphomutases); C513491:Pmm2 protein, mouse; C052799:phosphomannomutase