Quantitative trait locus mapping of genes regulating pulmonary PKC activity and PKC-alpha content.
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.
Department of Pharmaceutical Sciences and University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
L D
LD
Dwyer-Nield
B
B
Paigen
S E
SE
Porter
A M
AM
Malkinson
D000818:Animals; D001345:Autoradiography; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D003720:Densitometry; D005809:Genes, Regulator / Q000235:genetics*; D007178:Inbreeding; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics*; D016013:Likelihood Functions; D008126:Lod Score; D008163:Luminescent Measurements; D008168:Lung / Q000737:chemistry / Q000201:enzymology*; D051379:Mice; D008815:Mice, Inbred Strains; D011493:Protein Kinase C / Q000032:analysis / Q000235:genetics*; D051571:Protein Kinase C-alpha; D019655:Quantitative Trait, Heritable; D012333:RNA, Messenger / Q000032:analysis
D007527:Isoenzymes; D012333:RNA, Messenger; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha