Quantitative trait locus mapping of genes regulating pulmonary PKC activity and PKC-α content

Publisher Website
Google Scholar
Abstract
Strain A/J mice, which are predisposed to experimentally induced asthma and adenocarcinoma, have the lowest pulmonary protein kinase (PK) C activity and content among 22 inbred mouse strains. PKC in neonatal A/J mice is similar to that in other strains, so this difference reflects strain-dependent postnatal regulation. PKC activity is 60% higher in C57BL/6J (B6) than in A/J lungs, and the protein and mRNA concentrations of PKC-α, the major pulmonary PKC isozyme, are two- to threefold higher in B6 mice. These differences result from more than a single gene as assessed in F1, F2, and backcross progeny of B6 and A/J parents. Quantitative trait locus (QTL) analysis of 23 A×B and B×A recombinant inbred strains derived from B6 and A/J progenitors indicates a major locus regulating lung PKC-α content that maps near the Pkcα structural gene on chromosome 11 ( D11MIT333; likelihood ratio statistic = 12.5) and a major locus controlling PKC activity that maps on chromosome 3 ( D3MIT19; likelihood ratio statistic = 15.4). The chromosome 11 QTL responsible for low PKC-α content falls within QTLs for susceptibilities to lung tumorigenesis and ozone-induced toxicity.