title: Generation of a LacZ reporter transgenic mouse line for the stereological analysis of oligodendrocyte loss in galactosylceramidase deficiency.
abstract: Krabbe's disease is a leukodystrophy resulting from deficiency of galactosylceramidase and the accumulation of galactosylsphingosine (psychosine) in the nervous system. Psychosine is believed to cause central demyelination by killing oligodendrocytes. Quantitative analysis of this process is lacking. To address this, we generated a new transgenic reporter twitcher line in which myelinating oligodendrocytes are genetically marked by the expression of LacZ under control of the myelin basic protein (MBP) promoter. MBP-LacZ-twitcher transgenic mice were used for unbiased stereological quantification of β-galactosidase+oligodendrocytes in the spinal cord. As expected, we found decreased numbers of these cells in mutant cords, paralleling the severity of clinical disease. The decrease of oligodendrocytes does not correlate well with the increase of psychosine. The new MBP-LacZ-twitcher line will be a useful genetic tool for measuring changes in oligodendrocyte numbers in different regions of the mutant CNS and in preclinical trials of therapies to prevent demyelination. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Hongling
authors.initials: H
authors.lastname: Zhu
authors.affiliation: San Raffaele Scientific Institute, Milano, Italy.|Hunter James Kelly Research Institute, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ornaghi
authors.affiliation: Hunter James Kelly Research Institute, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
authors.forename: Sophie
authors.initials: S
authors.lastname: Belin
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Givogri
authors.affiliation: Hunter James Kelly Research Institute, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wrabetz
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois. ebongarz@uic.edu.
authors.forename: Ernesto R
authors.initials: ER
authors.lastname: Bongarzone
mesh_terms: D000375:Aging; D000818:Animals; D002478:Cells, Cultured; D017930:Genes, Reporter / Q000235:genetics; D007763:Lac Operon / Q000235:genetics*; D007965:Leukodystrophy, Globoid Cell / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009154:Mutation; D009185:Myelin Proteins / Q000096:biosynthesis / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism; D009836:Oligodendroglia / Q000473:pathology*; D011609:Psychosine / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D009185:Myelin Proteins; D011609:Psychosine; D001616:beta-Galactosidase
keywords: Krabbe's disease; demyelination; oligodendrocytes; psychosine