title: Monitoring the CNS pathology in aspartylglucosaminuria mice.
abstract: Aspartylglucosaminuria (AGU) is a recessively inherited lysosomal storage disorder caused by the deficiency of the aspartylglucosaminidase (AGA) enzyme. The hallmark of AGU is slowly progressing mental retardation but the progression of brain pathology has remained uncharacterized in humans. Here we describe the long-term follow-up of mice carrying a targeted AGU-mutation in both alleles. Immunohistochemistry, histology, electron microscopy, quantitative magnetic resonance imaging (MRI) and behavioral studies were carried out to evaluate the CNS affection of the disease during development. The lysosomal storage vacuoles of the AGA -/- mice were most evident in central brain regions where MRI also revealed signs of brain atrophy similar to that seen in the older human patients. By immunohistochemistry and MRI examinations, a subtle delay of myelination was observed in AGA -/- mice. The life span of the AGA -/- mice was not shortened. Similar to the slow clinical course observed in human patients, the AGA -/- mice have behavioral symptoms that emerge at older age. Thus, the AGU knock-out mice represent an accurate model for AGU, both histopathologically and phenotypically.
authors.affiliation: Department of Human Molecular Genetics, National Public Health Institute Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Tenhunen
authors.forename: A
authors.initials: A
authors.lastname: Uusitalo
authors.forename: T
authors.initials: T
authors.lastname: Autti
authors.forename: R
authors.initials: R
authors.lastname: Joensuu
authors.forename: M
authors.initials: M
authors.lastname: Kettunen
authors.forename: R A
authors.initials: RA
authors.lastname: Kauppinen
authors.forename: S
authors.initials: S
authors.lastname: Ikonen
authors.forename: M E
authors.initials: ME
authors.lastname: LaMarca
authors.forename: M
authors.initials: M
authors.lastname: Haltia
authors.forename: E I
authors.initials: EI
authors.lastname: Ginns
authors.forename: A
authors.initials: A
authors.lastname: Jalanko
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000818:Animals; D054880:Aspartylglucosaminuria; D001227:Aspartylglucosylaminase / Q000652:urine; D001522:Behavior, Animal / Q000502:physiology; D002490:Central Nervous System / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008607:Intellectual Disability / Q000201:enzymology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008991:Monitoring, Physiologic / Q000379:methods*; D009186:Myelin Sheath / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D001227:Aspartylglucosylaminase