A susceptibility gene for alveolar lung tumors in the mouse maps between Hsp70.3 and G7 within the H2 complex

Abstract

Lung tumor susceptibility (LTS) in the mouse is influenced by multiple loci within the H2 complex. We compared the LTS of two H2 congenic strains with intra H2 recombinations, B10.A(1R) and B10.A(2R), whose genetic difference has been reduced to a region of approximately 50 kilobases within the C4-H2D interval, between Hsp70.3 and G7. After transplacental induction with N-ethyl-N-nitrosourea the load of alveolar lung tumors in strain B10.A(2R) is significantly higher than in strain B10.A(1R) (P < 0.001). For papillary tumors no significant differences were observed. We conclude that the alveolar lung tumor load is influenced by an LTS gene located within the Hsp70.3-G7 interval.

Epithelial NF-κB activation promotes urethane-induced lung carcinogenesis

“…Second, TNF-␣ and IL-10 haploinsufficient mice display altered susceptibility to chemical-induced lung tumor formation (30). Third, genes responsible for the lung inflammatory response cosegregate with genes conferring susceptibility to chemical lung tumorigenesis within pulmonary adenoma susceptibility genetic loci (38), and the murine TNF-␣ gene has been identified as a strong candidate within the pulmonary adenoma susceptibility-2 locus (39,40). In our studies, inflammatory cell influx, increased TNF-␣ and/or IL-12p70 production, and activation of NF-B were identified in the lungs of mouse strains susceptible to urethane tumorigenesis (FVB and BALB/c), but not of a resistant strain (C57B6).…”

A novel locus affecting serum levels of IgG2a maps to the murine H2 region

“…B10.A(1R) and B10.A(2R) mice have been used to map the gene responsible for corticoid‐induced cleft palate ( Gasser et al. , 1988 ), vitamin A‐enhanced cleft palate ( Tyan & Tyan, 1993) and eye defects (microphthalmia and anophthalmia) ( Tyan, 1992), resistance to alveolar lung tumours ( Fijneman et al. , 1995 ) and orchitis ( Snoek et al.…”

Genetic susceptibility to HPV infection and cervical cancer

“…An increased risk for death or severe neurological disease due to cerebral malaria was associated with the TNF2 allele (46), a variant of the TNF-a gene promoter region, located in the MHC class III region. A susceptibility gene for alveolar lung tumors in the mouse was mapped to the H-2 complex class III region (47).…”