Quantitative trait locus mapping of genes regulating pulmonary PKC activity and PKC-alpha content.
Autoradiography, Chemiluminescence, Chromosome-Mapping, Crosses-Genetic, Densitometry, Genes-Regulator, Inbreeding, Isoenzymes, Likelihood-Functions, Lod-Score, Lung, Mice, Mice-Inbred-Strains, Protein-Kinase-C, Quantitative-Trait, RNA-Messenger, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S
Am J Physiol Lung Cell Mol Physiol 2000 Aug; 279(2):L326-32.
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-alpha, 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 F(1), F(2), and backcross progeny of B6 and A/J parents. Quantitative trait locus (QTL) analysis of 23 AxB and BxA recombinant inbred strains derived from B6 and A/J progenitors indicates a major locus regulating lung PKC-alpha content that maps near the Pkcalpha 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-alpha content falls within QTLs for susceptibilities to lung tumorigenesis and ozone-induced toxicity.
Dwyer, Nield L.; Paigen, B; Porter, S E.; and Malkinson, A M., " Quantitative trait locus mapping of genes regulating pulmonary PKC activity and PKC-alpha content." (2000). Faculty Research 2000 - 2009. 104.