Expression of mKNG1 and mKNG 2 in Mice

High and Low kininogen are precursors for kinin hormones and participates in activation of contact system. In the human, these proteins originate from a single gene. However, in the mouse two highly homologous kininogen genes (mKNG1, mKNG2) exist and are expressed in a tissue specific manner. The role of these genes in murine development and homeostasis has not been determined. We characterized the expression of each of these genes in vivo in wild type mice and mice in which mKNG1 has been deleted. mKNG1 yields three splice variants: HK1, LK1 and HK1ÄD5, a high molecular weight isoform that lacks the portion of exon 10 encoding Thr400–Asp582 of HK1 domains 5 and 6. All three proteins were present in plasma, as well as liver, lung, spleen and thymus, but neither kidney nor brain of wild type animals. To define the expression of mKNG2 we utilized mKNG1 deficient mice. In this animals, we were unable to detect HK2 or HK2ÄD5 proteins in plasma or tissues; however the LK2 protein was found in plasma. These findings suggest that mKNG1 gene products (HK, LK and HKÄD5) may have functional roles not only in plasma, but in specific murine tissues where they are highly expressed. In addition, these findings also suggest a predominant role for mKNG1 in mice, as this gene was more broadly and robustly expressed than mKNG2. Finally, the reason why mKNG2 does not yield an HK2 isoform suggests differential regulation of splicing of these two genes.