Reference SummaryBelinsky SA, Carcinogenesis 1997 Jan;18(1):115-20


Deletion and differential expression of p16INK4a in mouse lung tumors.


Belinsky SA; Swafford DS; Middleton SK; Kennedy CH; Tesfaigzi J












Recent allelotyping of chemical-induced lung tumors in hybrid mice has detected loss of heterozygosity on chromosome 4 in a region involving the interferon-alpha (IFN-alpha) gene cluster that is syntenic to human chromosome 9p21-22, the location of the p16(INK4a) (p16) and p15(INK4b) (p15) tumor suppressor genes, The purpose of the current investigation was to characterize the expression of p16 and p15 in lung tumors and tumor-derived cell lines induced in A/J mice by exposure to the tobacco- specific nitrosamine, 4-methyl-nitrosamino-1-(3-pyridyl)-1- butanone (NNK), Expression of p16 and p15 was detected in all primary lung tumors; however, levels of expression of p16 differed by up to 15-fold between tumors. This is the first study to note a marked difference in the expression of the p16 gene in primary lung tumors, The apparent low levels of expression seen in approximately half of the tumors was not attributed to deletion, mutation or methylation of the p16 gene, Conversely, the high levels of p16 expression were not the result of effects on the retinoblastoma gene (Rb) or cyclin D1 proteins but most likely in response to a dysfunction elsewhere within this pathway, In contrast to the detection of p16 expression in primary tumors, this gene was deleted in all four cell lines, Three of four cell lines also showed loss of the p15 gene, Mapping of these homozygous deletions on chromosome 4 revealed that the p16 gene resides near the D4MIT77 marker, which is located approximately 12 cM proximal to the IFN-alpha gene cluster, thereby implicating the p16 gene as one of the targets within the allelic deletions detected previously in primary lung tumors from hybrid mice.


J:38603 – MGI References
9054597 – National Library of Medicine/PubMed

Strain Notes

Strain Note
A/J Expression of the normal allele of the Cdkn2a gene was reported to be slightly expressed in the lungs of these mice.
The wild type alleles of the Ccnd1, Cdkn2a, Cdkn2b, and Rb1 genes were reported to be expressed in the lungs of these mice.


Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
A/J Lung adenocarcinoma
  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)