Genetic regulation of thermostability of mouse submaxillary gland renin

Renin activity in the mouse submaxillary gland is under complex hormonal and genetic control. Basal and induced renin levels are regulated by Rnr, a gene located on Chromosome 1. Mice homozygous for Rnrs or Rnrb alleles have high or low levels of submaxillary gland renin, respectively. We have utilized inbred strain-specific differences in renin stability at 60 degrees C to determine the relationship between Rnr and the renin structural gene. Renin from 13 strains carrying the Rnrb allele is more stable (mean t1/2 = 13.6 +/- S.E. 0.9 min) than that from 24 strains carrying the Rnrs allele (mean t1/2 = 2.1 +/- 24 strains carrying the Rnrs allele (mean t1/2 = 2.1 +/- S.E. 0.04 min). Thermostability was not affected by purification or dilution of the enzyme, or by mixing labile and stable renin prior to heating. Fifty-five informative recombinant inbred mouse strains were also examined, and inactivation of renin at 60 degrees C in each instance resembled one or the other progenitor strain. Furthermore, when the Rnrs alleles is transferred to the genetic background of an Rnrb type strain, renin activity from the congenic inbred strain is both high and thermolabile. Thus, there is complete concordance between thermolability and Rnrs. Alloantibody elicited by submaxillary gland renin from an Rnrs/Rnrs strain blocks the activity of Rnrs but not Rnrb type renin. These results indicate close linkage or identity between a gene that regulates renin activity in the mouse submaxillary gland and a gene that influences the structure of the renin molecule. Such a relationship is compatible with several models for the genetic control of renin activity in this tissue.