Guanylate Cyclase 1 Alpha 1 (GUCY1a1)

Gucy1a1 and Gucy1b1, have recently been mapped close to Npr1 in the rat genome and therefore are also candidate genes. All 3 of these genes affect cGMP production. ANP binding results in increased cGMP mediated through the Npr1 gene product, an effect also produced by NO mediated through the Gucy1a1 and Gucy1b1 gene products. The GH rat has recently been shown to rapidly develop a strokelike syndrome when given a NO synthase (NOS) inhibitor. A defect in Npr1, or possibly Gucy1a1 or Gucy1b1, may limit compensatory cGMP in the face of NOS inhibition and account for the development of stroke engendered by NOS inhibition in the GH rat. Whereas Npr1, Gucy1a1, and Gucy1b1 are in close proximity in the rat genome, in humans NPR1 is on chromosome 1q21-q22, while GUCY1B3 and GUCY1A3, the human homologues of Gucy1a1 and Gucy1b1, are on chromosome 4 at q31.3-q33.