Molecular genetics of XXXX .

@entity1 @entity1117 @entity535 @entity1112 @entity1110 @entity379 @entity74 @entity1111 @entity224
@entity1117 is an @entity74 characterized by the failure of phagocytic cells to produce @entity224 upon the ingestion of microorganisms due to a lesion in a membrane-associated @entity1110 -oxidase. The components of the oxidase have been incompletely characterized by standard biochemical approaches. A genetic strategy has recently led to the identification of the gene affected in the common @entity1112 without reference to its protein product. The @entity1111 gene, assigned to chromosome position Xp21.1, encodes a phagocyte-specific RNA transcript that is mutated in @entity1 with @entity1111 . Antisera directed toward the predicted protein product of the @entity1111 gene recognize a 90 kD membrane glycoprotein, which corresponds to the larger subunit of the phagocyte b-cytochrome heterodimer. The recent genetic and biochemical findings provide an explanation for the consistent absence of the b-cytochrome spectrum in @entity1111 , and establish this cytochrome as an essential component of the phagocyte oxidase. The primary @entity535 sequence of both the 90 kD b-cytochrome subunit and the 22 kD subunit (cloned as the cDNA using a specific antisera) have no significant similarity to other proteins, including previously studied cytochromes. As both subunits of the b-cytochrome heterodimer are absent in @entity1111 , despite a @entity74 of only the larger polypeptide, a close interaction between the two subunits may be important for b-cytochrome stability and function. Expression of the b-cytochrome large subunit mRNA is increased by @entity379 , an important macrophage activator. Partial or complete restoration of oxidase activity in some @entity1111 @entity1 treated with @entity379 suggests new therapeutic approaches in the management of this disorder. Molecular reagents prepared from the cloned @entity1111 cDNA or gene may prove to be clinically useful in prenatal diagnosis and may provide a basis for somatic gene therapy in future.
