Fig. 1: Ectopic human TYMS (hTS) enhances tumor growth and shortens survival in heterozygous Ink4a/Arf mice.
From: TYMS promotes genomic instability and tumor progression in Ink4a/Arf null background
A Breeding scheme to generate hTS/Ink4a/Arf +/– mice by crossing hTS transgenic mice with Ink4a/Arf −/− mice. Location of forward and reverse primers for the detection of hTS transgene and Ink4a/Arf locus are depicted by arrows. Detection of the wild-type allele was performed as described in Methods. Representative PCR analysis of gDNA extracted from mice tails shows presence (+) or absence (–) of 406 bp hTS band or wild-type 278 bp or deleted 318 bp Ink4a/Arf bands. CMV cytomegalovirus promoter, NeoR neomycin resistance cassette. B Ectopic hTS decreases survival in heterozygous Ink4a/Arf +/– mice. Kaplan-Meir survival analysis of control Ink4a/Arf +/– (broken line, n = 14) and hTS/Ink4a/Arf +/– (solid line, n = 15) mice. hTS/Ink4a/Arf +/– median survival was 313 days (95% CI, 240–359 days) compared to 411.5 days (95% CI, 217–542 days) in Ink4a/Arf +/– mice (*P = 0.032 by log-rank Mantel-Cox test). C Incidence of histiocytic sarcoma, lymphoma and fibrosarcoma is increased by ectopic hTS. Number and percentage of mice with tumors in Ink4a/Arf +/– and hTS/Ink4a/Arf +/– are shown.
