| First Author | Wilson C | Year | 2005 |
| Journal | Cancer Res | Volume | 65 |
| Issue | 22 | Pages | 10179-82 |
| PubMed ID | 16288003 | Mgi Jnum | J:103410 |
| Mgi Id | MGI:3609443 | Doi | 10.1158/0008-5472.CAN-05-2688 |
| Citation | Wilson C, et al. (2005) Induction of renal tumorigenesis with elevated levels of somatic loss of heterozygosity in Tsc1+/- mice on a Blm-deficient background. Cancer Res 65(22):10179-82 |
| abstractText | A Bloom's deficient mouse model (Blm(m3/m3)) has been shown to induce colorectal tumorigenesis when crossed with Apc+/Min mice. Here, we investigated whether the Blm(m3/m3) genotype could induce tumorigenesis in extracolonic tissues in tuberous sclerosis 1-deficient (Tsc1+/-) mice that are predisposed to renal cystadenomas and carcinomas. Genotyping of offspring from Tsc1+/- Blm+/m3 intercrosses showed that a approximately 24% excess of Tsc1+/- over Tsc1+/+ mice died before weaning (P = 0.016), although Blm deficiency had no cumulative effect on Tsc1+/- survival. Tsc1+/- Blm(m3/m3) mice had significantly more macroscopic and microscopic renal lesions at 3 to 6 months compared with Tsc1+/- Blm+/m3 mice (P =0.0003 and 0.0203, respectively), and their tumors showed significantly increased levels of somatic loss of heterozygosity (LOH) of the wild-type Tsc1 (Tsc1wt) allele compared with those from Tsc1+/- Blm+/+ mice (P < 0.0001). Tsc1+/- Blm+/m3 mice did not show significantly more renal lesions compared with Tsc1+/- Blm+/+ animals; however, their lesions still showed significantly increased levels of somatic LOH of the Tsc1wt allele (P = 0.03). Ninety-five percent (19 of 20) of lesions from Tsc1+/- Blm+/m3 mice retained the wild-type Blm (Blm(wt)) allele, indicating that the increased somatic LOH at Tsc1 was mediated by Blm haploinsufficiency. Renal lesions from a Blm-deficient background stained positively with anti-phospho-S6 ribosomal protein (Ser240/244), suggesting that these lesions develop through the normal pathway of Tsc-associated tumorigenesis. This work shows the use of the Blm(m3/m3) mice for inducing renal tumorigenesis, and the high levels (approximately 87%) of LOH in the resultant tumors will help facilitate mapping of loci involved in tumor progression. |
