Respiratory timing is governed by two genes in murime inbred strains

Gene regulation has been shown to govern phenotypic differences in baseline breathing patterns between C3H/HeJ (C3) and C57BL/6J (B6) mice. The present study examined twelve BXH recombinant inbred (RI) strains derived from C3 and B6 progenitors to determine the specific genes regulating differential respiratory timing; i.e., breathing frequency (f) and inspiratory time (T,). In each of 82 mice, baseline breathing pattern was assessed five times using whole-body plethysmography to measure tidal volume, f, and T,. As compared to the progenitors, three distinct phenotypes were evident in the BXH RI strain distribution pattern (SDP). With respect to f and t each of the progenitors was represented by at least one RI strain, and an intermediate phenotype was detected. These findings are consistent with the hypothesis that strain-specific differences in respiratory timing can be best explained by a two-gene loci model. Linkage analyses comparing the BXH RI SDP for respiratory timing to a library of gene markers suggested that one of two genes mapped to murine chromosome 3 (significant concordance with gene marker D3MÜ7). This chromosomal region encodes a gene cluster of neuroreceptors involved in respiratory control.