title: Tissue distribution of the murine phosphomannomutases Pmm1 and Pmm2 during brain development.
abstract: The most common type of the congenital disorders of glycosylation, CDG-Ia, is caused by mutations in the human PMM2 gene, reducing phosphomannomutase (PMM) activity. The PMM2 mutations mainly lead to neurological symptoms, while other tissues are only variably affected. Another phosphomannomutase, PMM1, is present at high levels in the brain. This raises the question why PMM1 does not compensate for the reduced PMM2 activity during CDG-Ia pathogenesis. We compared the expression profile of the murine Pmm1 and Pmm2 mRNA and protein in prenatal and postnatal mouse brain at the histological level. We observed a considerable expression of both Pmms in different regions of the embryonic and adult mouse brain. Surprisingly, the expression patterns were largely overlapping. This data indicates that expression differences on the cellular and tissue level are an unlikely explanation for the absence of functional compensation. These results suggest that Pmm1 in vivo does not exert the phosphomannomutase-like activity seen in biochemical assays, but either acts on as yet unidentified specific substrates or fulfils entirely different functions.
authors.affiliation: Division of Clinical Genetics, Center for Human Genetics, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Cromphout
authors.forename: L
authors.initials: L
authors.lastname: Keldermans
authors.forename: A
authors.initials: A
authors.lastname: Snellinx
authors.forename: J F
authors.initials: JF
authors.lastname: Collet
authors.forename: S
authors.initials: S
authors.lastname: Grünewald
authors.forename: N
authors.initials: N
authors.lastname: De Geest
authors.forename: R
authors.initials: R
authors.lastname: Sciot
authors.forename: E
authors.initials: E
authors.lastname: Vanschaftingen
authors.forename: J
authors.initials: J
authors.lastname: Jaeken
authors.forename: G
authors.initials: G
authors.lastname: Matthijs
authors.forename: D
authors.initials: D
authors.lastname: Hartmann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D017875:Phosphotransferases (Phosphomutases) / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase