title: Mutation in the gene encoding lysosomal acid phosphatase (Acp2) causes cerebellum and skin malformation in mouse.
abstract: We report a novel spontaneous mutation named nax in mice, which exhibit delayed hair appearance and ataxia in a homozygote state. Histological analyses of nax brain revealed an overall impairment of the cerebellar cortex. The classical cortical cytoarchitecture was disrupted, the inner granule cell layer was not obvious, the Purkinje cells were not aligned as a Purkinje cell layer, and Bergmann glias did not span the molecular layer. Furthermore, histological analyses of skin showed that the hair follicles were also abnormal. We mapped the nax locus between marker D2Mit158 and D2Mit100 within a region of 800 kb in the middle of chromosome 2 and identified a missense mutation (Gly244Glu) in Acp2, a lysosomal monoesterase. The Glu244 mutation does not affect the stability of the Acp2 transcript, however it renders the enzyme inactive. Ultrastructural analysis of nax cerebellum showed lysosomal storage bodies in nucleated cells, suggesting progressive degeneration as the underlying mechanism. Identification of Acp2 as the gene mutated in nax mice provides a valuable model system for studying the role of Acp2 in cerebellum and skin homeostasis.
authors.affiliation: Institute of Human Genetics, University of Goettingen, Heinrich-Dueker-Weg 12, 37073, Goettingen, Germany.
authors.forename: Ashraf U
authors.initials: AU
authors.lastname: Mannan
authors.forename: Elena
authors.initials: E
authors.lastname: Roussa
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kraus
authors.forename: Micheal
authors.initials: M
authors.lastname: Rickmann
authors.forename: Joerg
authors.initials: J
authors.lastname: Maenner
authors.forename: Karim
authors.initials: K
authors.lastname: Nayernia
authors.forename: Kerstin
authors.initials: K
authors.lastname: Krieglstein
authors.forename: André
authors.initials: A
authors.lastname: Reis
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Engel
mesh_terms: D000135:Acid Phosphatase; D000595:Amino Acid Sequence; D000818:Animals; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000473:pathology; D002531:Cerebellum / Q000002:abnormalities*; D008040:Genetic Linkage; D018859:Hair Follicle / Q000002:abnormalities; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics*; D008247:Lysosomes / Q000201:enzymology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics*; D012868:Skin Abnormalities / Q000235:genetics*; D013329:Structure-Activity Relationship
chemical_list: D007527:Isoenzymes; D000135:Acid Phosphatase; C520785:Acp2 protein, mouse; D017027:Protein Tyrosine Phosphatases