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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Localization of cells in the rat brain expressing fumarylacetoacetate hydrolase, the deficient enzyme in hereditary tyrosinemia type 1.

Fumarylacetoacetate hydrolase (FAH) is the terminal enzyme in the catabolic pathway of tyrosine. This enzyme which is mainly expressed in the liver and kidney is deficient in hereditary tyrosinemia type 1. As some affected individuals present neurologic abnormalities, we studied the expression of FAH in the rat and human brain. The FAH gene was shown to be expressed in the rat brain by immunoblot and Northern blot analysis. The FAH protein was also detected in human brain by the immunoblot assay. An immunohistochemical study was undertaken to localize the FAH-producing cells in the rat central nervous system. This analysis showed that the majority of FAH-producing cells are localized in the axonal nerve fibers of the white matter, although positive cells could also be found throughout the brain. The greatest number of FAH-positive cells were found in structures consisting essentially of white matter, such as the corpus callosum. This specific localization in the white matter indicates that some type of glial cells are responsible for the expression of the FAH protein in the rat central nervous system. The characteristic linear organization found in some of the FAH-positive cells in the corpus callosum suggests that these glial cells are oligodendrocytes. These findings are discussed with respect to the neurologic symptoms observed in some tyrosinemia patients.[1]


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