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Chromosomal substitution strains indicate genetic determinants of the hypercapnic ventilatory response on rat chromosome 10
Author(s) -
Hodges Matthew Robert,
Dwinell Melinda R,
Jacob Howard J.,
Cowley Allen W.,
Forster Hubert V.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.847.11
Brown Norway (BN) rats exhibit a blunted (+40%) hypercapnic ventilatory response (HVR) compared to other inbred strains, such as the Dahl Salt‐sensitive (SS; +200%) and Fawn‐hooded hypertensive (FHH; +150%) rats, despite exhibiting little or no differences in the ventilatory responses to hypoxia or moderate exercise. In an effort to determine the contributions of specific chromosomes to phenotypic differences among these strains, chromosomal substitution (consomic) strains were generated and studied by the Program for Genomic Applications (PGA) at MCW. Here, we performed a meta‐analysis of the publically‐available PGA data from 44 consomic rat strains in which a single BN chromosome was introgressed into the genetic background of either the SS or FHH strains. We found that multiple consomic strains exhibited a more “BN‐like” ventilatory response to hypercapnia, indicated by a significantly lower minute ventilation (V E ), breathing frequency (f) or tidal volume (V T ) while breathing 7% CO 2 . However, the chromosomes that showed significant effects on the HVR varied by both gender and background strain. In contrast, all rats receiving BN chromosome 10 (male or female and SS or FHH background) demonstrated a significantly blunted HVR compared to the parental SS and FHH rats, and equal to the parental BN HVR. These data indicate that a major determinant of the HVR resides on rat chromosome 10. Supported by NIH HL097033.