Summary
The brindled mutation is an X-linked neurological mutation in mice. Male mice hemizygous for the brindled gene have metabolic defects homologous with kinky hair disease in humans. Neuropathologically, the mutation is characterized by extensive neuronal degeneration associated with pronounced mitochondrial changes in cerebral cortex and abnormal arborization of Purkinje cell dendrites, which are most pronounced in the rostral vermis or anterior lobules.
In the cerebellum of female mice heterozygous for brindled gene, Purkinje cells with abnormal dendritic arborization and with unusually enlarged mitochondria were also observed. Morphological changes in affected Purkinje cells in young heterozygotes were similar to those of young hemizygotes. However, in older heterozygotes, the changes were far less conspicuous, indicating the presence of some extrinsic factor(s) to compensate expression of the mutant gene in heterozygous brains.
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References
Benjamins JA, Skoff RP, Beyer K (1984) Biochemical expression of mosaicism in female mice heterozygous for the jimpy gene. J Neurochem 42:487–492
Camakaris J, Mann JR, Danks DM (1979) Copper metabolism in mottled mouse mutants: copper concentrations in tissue during development. Biochem J 180:597–604
Fraser AS, Sobey S, Spieev CC (1953) Mottled, a sex-modified lethal in the house mouse. J Genet 51:219–222
Holstein TJ, Fung RQ, Queredo WC Jr, Bienieki TC (1979) Effect of altered copper metabolism induced by mottled alleles and diet on mouse tyrosinase (40662). Proc Soc Exp Biol Med 162:264–268
Hunt DM (1974) Primary defect in copper transport underlies mottled mutant in the mouse. Nature 249:852–854
Inoue M, Oda S (1980) Strain-specific variations in the folial pattern of the mouse cerebellum. J Comp Neurol 190:357–362
Lyon MF (1961) Gene action in the X-chromosome of the mouse (Mus musculus L). Nature 190:372–373
Lyon MF (1962) Sex chromatin and gene action in the mammalian X-chromosome. Am J Hum Genet 14:135–148
Lyon MF (1972) X-Chromosome inactivation and development patterns in mammals. Brain Res 47:1–35
Mann JR, Camakaris J, Danks DM, Walliczek EG (1979) Copper metabolism in mottled mouse mutant. Copper therapy of brindled (MObr) mice. Biochem J 180:605–612
Nagara H, Yajima K, Suzuki K (1980) An ultrastructural study of the cerbellum of the brindled mouse. Acta Neuropathol (Berl) 52:41–50
Nagara H, Yajima K, Suzuki K (1981) The effect of copper supplementation on the brindled mouse. A clinico-pathological study. J Neuropathol Exp Neurol 40:428–446
Prins HW, Van den Hamer CJA (1979) Primary biochemical defect in copper metabolism in mice with a recessive X-linked mutation analogous to Menkes' disease in man. J Inorg Biochem 10:19–27
Prohaska JR, Wells WW (1974) Copper deficiency in the developing rat brain: a possible model for Menkes' steely-hair disease. J Neurochem 23:91–98
Rosenfeld J, Friedrich VL Jr (1984) Hypomyelination and recovery on the myelin deficit in heterozygous jimpy mice. Int J Dev Neurosci 2:21–32
Sholl DA (1953) Dendritic organization in the neurons of the visual cortices of the cat. J Anat 87:387–407
Skoff R, Montgomery IN (1981) Expression of mosaicism in females heterozygous for jimpy. Brain Res 212:175–181
Wenk G, Suzuki K (1982) The effect of copper supplementation on the concentration of copper in the brain of the brindled mouse. Biochem J 205:485–487
Yajima K, Suzuki K (1979a) Neuronal degeneration in the brain of the brindled mouse. A light microscopic study. J Neuropathol Exp Neurol 38:35–46
Yajima K, Suzuki K (1979b) Neuronal degeneration in the brain of the brindled mouse. An ultrastructural study of the cerebral cortical neurons. Acta Neuropathol (Berl) 45:17–25
Yamano T, Suzuki K (1985) Abnormalities of Purkinje cell arborization in brindled mouse cerebellum-A Golgi study. J Neuropathol Exp Neurol 44:85–96
Yamano T, Paldino AM, Suzuki K (1985) Ultrastructural and morphometric studies on Purkinje cells of brindled mouse after administration of cupric chloride. J Neuropathol Exp Neurol 44:97–107
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Supported in part by research grants NS-03356, NS-10803, HD-01799 and a training grant for experimental neuropathology NS-07098 from the National Institutes of Health, U.S.P.H.S.
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Yamano, T., Suzuki, K. Cerebellar changes of the female mice heterozygous for brindled gene. Acta Neuropathol 69, 220–226 (1986). https://doi.org/10.1007/BF00688297
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DOI: https://doi.org/10.1007/BF00688297