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• W2058743419 abstract "The Pahenu2 mouse, created through ethylnitrosurea mutagenesis, is a model for phenylketonuria. These mice have elevated serum phenylalanine levels, hypopigmentation, and behavior and movement abnormalities, and female mice exhibit a maternal phenylketonuria syndrome. We evaluated the brains of adult and juvenile Pahenu2 mice for consistent, demonstrable lesions to elucidate various neuropathologic processes and to assess the efficacy of various treatment modalities such as AAV-mediated gene therapy. One aspect of the disease may involve the effect of hyperphenylalanemia on catecholamine function. High levels of phenylalanine inhibit enzymes that are important in the conversion of tyrosine and tryptophan to their respective neurotransmitter derivatives, including dopamine. Therefore, assessment of dopaminergic regions was of interest in this study. Histologic evaluation of juvenile and adult brains revealed an increased cellular density as early as 4 wk of age in the middle to posterior hypothalamus and substantia nigra. The infiltrating cells showed immunoreactivity for CD11b and had morphologic characteristics of macrophages. There was marked expression of inducible nitric oxide synthase in these dopaminergic regions that co-localized to CD11b-positive cells. The CD11b-positive cells and increased inducible nitric oxide synthase expression in these regions may function in a neuroregulatory manner to compensate for alterations in dopamine metabolism." @default.
• W2058743419 created "2016-06-24" @default.
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• W2058743419 date "2005-08-01" @default.
• W2058743419 modified "2023-10-18" @default.
• W2058743419 title "Pathologic and Immunohistochemical Findings in Hypothalamic and Mesencephalic Regions in the Pahenu2 Mouse Model for Phenylketonuria" @default.
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• W2058743419 doi "https://doi.org/10.1203/01.pdr.0000170000.78670.44" @default.
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