Several recent studies have demonstrated that ablation of genes of the
renin-angiotensin system can have wide-ranging and sometimes unexpect
ed effects. Renin is directly involved in blood pressure regulation an
d is encoded by a single gene in most mammals. Wild mouse strains and
some inbred laboratory strains have a duplicated renin gene (Ren-2), t
he physiological significance of which is unclear. Significant differe
nces exist in the structure and expression of these renin genes, but a
s yet, no distinct biological function that distinguishes these genes
has been defined. We have used gene targeting to discover the effects
of inactivating the duplicated (Ren-2) gene in strain 129 mice, and we
show that mice lacking the Ren-2 gene are viable and healthy. There a
ppear to be no histopathological differences in renin-expressing tissu
es between Ren-2-null mice and their controls. Studies of our Ren-2-nu
ll mice allow, for the first time, a direct evaluation of the ability
of the Ren-1(d) gene to regulate blood pressure in the absence of expr
ession of the Ren-2 enzyme. We observed no alteration to blood pressur
e in adult mice homozygous for the mutated Ren-2 gene, even though the
concentration of active renin is increased and of prorenin is decreas
ed in plasma of these mice. Ren-1(d) is therefore capable of regulatin
g normal blood pressure and despite a different tissue expression prof
ile, is functionally equivalent to Ren-1(c).