title: Abnormal movements in brindled mutant mouse heterozygotes: as related to the development of their offspring--biochemical and morphological studies.
abstract: As a possible preventive measure for brain dysfunction in Menkes disease, prenatal treatment by maternal administration of zinc, vitamin E and copper was examined in brindled mutant mice. During pregnancy and lactation, female heterozygous mice received 20 ppm zinc or 0.004% alpha-tocopherol acetate (vitamin E) throughout and 6 ppm copper from gestational day 13 in the drinking fluid, ad libitum. The maternal administration of zinc and vitamin E, as antioxidants, or copper resulted in decreased fetal and neonatal death of offspring, especially those of hemizygous males, as compared with the administration of water only. When offspring did not grow, maternal abnormal movements, which comprised rotatory movements of high speed with tremor and ataxia, were frequently observed. In the heterozygotes with abnormal movements, the level of lipid peroxidation in cerebrum and the concentration of copper in kidney were much higher than those in the heterozygotes with normal movement. Morphologically, in cerebellum of the heterozygotes with abnormal movements, the loss of Purkinje cells, abundance of lipofuscin granules and abnormal mitochondria or degenerative bodies of high electron density were frequently observed, as compared with heterozygotes with normal movement. These findings suggest that the development of hemizygous male mice may be influenced by both copper and oxygen radical metabolism.
authors.affiliation: Division of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Kasama
authors.forename: K
authors.initials: K
authors.lastname: Inomata
authors.forename: F
authors.initials: F
authors.lastname: Nasu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology / Q000473:pathology; D001923:Brain Chemistry; D003300:Copper / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D006579:Heterozygote; D007668:Kidney / Q000201:enzymology; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009069:Movement Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption; D011247:Pregnancy; D013482:Superoxide Dismutase / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
chemical_list: D003300:Copper; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV; D015032:Zinc