title: Transgenic mice expressing the human C99 terminal fragment of betaAPP: effects on cytochrome oxidase activity in skeletal muscle and brain.
abstract: In order to furnish a combined model of relevance to human inclusion-body myopathy and Alzheimer's disease, transgenic mice expressing human betaAPP-C99 in skeletal muscle and brain under the control of the cytomegalovirus/beta-actin promoter were produced (Tg13592). These transgenic mice develop Abeta deposits in muscles but not in brain. Cell metabolic activity was analyzed in brain regions and muscle by cytochrome oxidase (CO) histochemistry, the terminal enzyme of the electron transport chain. By comparison to age-matched controls of the C57BL/6 strain, CO activity was selectively increased in dark skeletal muscle fibers of Tg13592 mice. In addition, only increases in CO activity were obtained in those brain regions where a significant difference appeared. The CO activity of Tg13592 mice was elevated in several thalamic nuclei, including laterodorsal, ventromedial, and midline as well as submedial, intralaminar, and reticular. In contrast, the groups did not differ in most cortical regions, except for prefrontal, secondary motor, and auditory cortices, and in most brainstem regions, except for cerebellar (fastigial and interpositus) nuclei and related areas (red and lateral vestibular nuclei). No variation in cell density and surface area appeared in conjunction with these enzymatic alterations. The overproduction of betaAPP-C99 fragments in brain without (amyloidosis did not appear to affect the metabolic activity of structures particularly vulnerable in Alzheimer's disease.
authors.affiliation: Laboratoire de Pathologie Moléculaire et Cellulaire en Nutrition (EMI-INSERM 0014) and Service de Microscopie Electronique, Faculté de Médecine, Université Henri Poincaré, Nancy I, France. straziel@persmail.uhp-nancy.fr
authors.forename: C
authors.initials: C
authors.lastname: Strazielle
authors.forename: M
authors.initials: M
authors.lastname: Dumont
authors.forename: K
authors.initials: K
authors.lastname: Fukuchi
authors.forename: R
authors.initials: R
authors.lastname: Lalonde
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D002452:Cell Count; D048429:Cell Size / Q000235:genetics; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000201:enzymology*; D018979:Myositis, Inclusion Body / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D013788:Thalamus / Q000166:cytology / Q000201:enzymology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D003576:Electron Transport Complex IV