Structure and expression of the genes for major acute phase alpha 1-protein (thiostatin) and kininogen in the rat

Two major acute phase alpha 1-protein (alpha 1-MAP, also called thiostatin) genes, one kininogen gene and one structurally related pseudogene, were isolated from a Buffalo rat genomic library and characterized. Comparison of the nucleotide sequence in the 5' proximal flanking region (1 kilobase) of a strongly inducible alpha 1-MAP gene with that in the non-inducible rat kininogen gene showed an overall homology of 90%, with a small number of randomly distributed base changes. In the intron downstream of the exon coding for Ile-Ser-bradykinin, the two alpha 1-MAP genes contained sequence sections similar to the section in the human kininogen gene which codes for the carboxyl-terminal chain of high molecular weight kininogen. Various features of the DNA related to gene expression such as initiation and termination sites of transcription, receptor binding sites, a Z-DNA section, and exon/intron splicing sites were identified. mRNAs expressed by alpha 1-MAP and kininogen genes in liver were studied by RNA blot hybridization using specific oligonucleotide probes. The kininogen gene expressed two mRNA species, one coding for high molecular weight kininogen, the other coding for low molecular weight kininogen. The levels of the two kininogen mRNAs in liver did not increase during acute inflammation. Only one type of mRNA, similar in size to low molecular weight kininogen RNA, was expressed by each of the two alpha 1-MAP genes. The levels of both alpha 1-MAP mRNAs increased strongly during acute inflammation.