Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The macular mutant mouse shows X-linked recessive inheritance and its hemizygote (Ml/y) is considered to be an appropriate model of Menkes kinky hair disease (MKHD). In this study the homozygote (Ml/Ml) was bred by coupling CuCl2-treated Ml/y with Ml/+ and was clinically and neuropathologically examined. The Ml/Ml had white fur color and curly whiskers from day 3, showed ataxia and tonic seizure on day 8 and gradually lost weight after day 10. It died with severe emaciation around day 15. These clinical features were improved by CuCl2 injection. Quantitative analysis showed that the dendritic arborization of the pyramidal cell in the treated Ml/Ml was delayed on days 14, 20, 30, 45 and 90 in comparison with that of the age-matched +/y. In the cerebellum of the Ml/Ml on day 14, some of the Purkinje cells showed abnormal changes such as somal sprouts, spine-like structures on the surface of the soma and stem dendrites, thick stem dendrites, multiple focal swellings of the stem and distal dendrites, reduction in the size of dendritic trees and axonal focal swellings. These changes were gradually improved in the Ml/Ml with CuCl2 treatment after day 20, with the exception of the multiple focal swellings of the stem and distal dendrites. The dendritic focal swelling gradually decreased after day 45. These clinical and neuropathological features of the Ml/Ml are almost same as those of the Ml/y. In our mutant mouse, when the treated Ml/Ml is coupled with the treated Ml/y all offspring from the Ml/Ml are genetically Ml/y or Ml/Ml. Our study indicates that these fetal mice may be useful for studying the pathological and biochemical condition of prenatal MKHD.
 ...
PMID:Golgi study on the homozygote (Ml/Ml) of macular mutant mouse. 247 62

The macular mutant mouse was clinically and pathologically examined. The hemizygotes began to show white fur color and curly whiskers around postnatal day 3, then seizures and ataxia around day 8, while the normal littermates did not. The hemizygotes also increased weight gradually from birth to day 9, but then showed weight loss and died around day 15 with severe emaciation. These clinical features resembled those in Menkes kinky hair disease. There were no pathological changes in the cerebral cortex in the hemizygotes on day 7. On day 10, two to three clear vacuoles began to appear in a few neurons in the cerebrum. These neurons with vacuoles increased gradually in number and degenerative neurons were also observed by day 14. Ultrastructurally, they corresponded to giant abnormal mitochondria with an electron-lucent matrix and short peripherally located cristae. Other abnormal mitochondria, which were characterized by an electron-dense matrix with tubular or vesicular cristae, were also observed in the cerebral cortical neurons.
 ...
PMID:Clinico-pathological study on macular mutant mouse. 356 5

This study was undertaken to elucidate, using the Golgi method, the neuropathological change in the brain of the macular mutant mouse, whose hemizygote (Ml/y) is considered to be a model of Menkes kinky hair disease (MKHD). The hemizygote mice gradually lost weight after 10 days of age and died with emaciation and seizure around day 15. The normal littermate (+/y) was well developed. In the cerebrum, the arborization of pyramidal neurons in the layer V of the Ml/y was the same as that in the +/y on day 10. However, development of arborization in the Ml/y was delayed in comparison with that in the +/y on days 12 and 14. Purkinje cells with several somal sprouts were observed in the cerebellum in both the Ml/y and +/y on day 7. The somal sprouts in the +/y had regressed gradually by day 12, while they were still in the anterior and middle lobes of the Ml/y on day 14. Additionally, the trunks of Ml/y stem dendrites became thicker and a cactus formation was recognized on the branching portion of the dendrites on day 14. Arborization of these abnormal Purkinje cells was distinctly poor compared with that in the +/y. These results suggest that the growth of the neurons is delayed in the Ml/y and simultaneously their cytoskeletal developments are disturbed, especially in the Purkinje cells. There is a close similarity in many respects to the neuropathological change in MKHD.
 ...
PMID:Golgi study on brain of macular mutant mouse as a model of Menkes kinky hair disease. 357 90

Brindled mottled is a neurological mutant mouse. Hemizygous males have many clinical and biochemical features in common with kinky hair syndrome (KHS) in humans, and usually die around postnatal day 15, after severe emaciation. Neuronal mitochondrial abnormalities and neuronal degeneration in the cerebrum and cerebellum were constant neuropathological findings in this mutant. A single intraperitoneal injection of cupric chloride, 10 micrograms/g body weight, resulted in an improvement of clinical symptoms and prevention of neuronal degeneration. The degree of improvement was dependent on the date of injection, and day 7 to 10 postnatal appeared to the most effective date. The male hemizygotes which received cupric chloride injections at day 7 or 10 overcame the lethality, and no neuronal degeneration was detected in these mice, although neuronal mitochondrial changes were still persistent. However, following two injections at days 7 and 10, no abnormalities were detected in the cerebral cortical neurons. Even at the ultrastructural level, abnormal mitochondria were very scarce. In the cerebellum, however, mitochondrial changes in the Purkinje cells, particularly in the rostral portion, and generation of white matter were noted in these mice, which were clinically perfectly healthy, judging from the growth rate and behavior. However, cerebellar changes were far less in those which received additional injections later on. These observations indicate that, at least in brindled mutant mice, supplementation of copper is quite beneficial for clinical improvement and the prevention of neuropathological lesions, but the date of administration appears to have crucial importance.
 ...
PMID:The effect of copper supplementation on the brindled mouse: a clinico-pathological study. 719 26