Induction of renal tumorigenesis with elevated levels of somatic loss of heterozygosity in Tsc1+/- mice on a Blm-deficient background.
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.[1]References
- Induction of renal tumorigenesis with elevated levels of somatic loss of heterozygosity in Tsc1+/- mice on a Blm-deficient background. Wilson, C., Idziaszczyk, S., Colley, J., Humphreys, V., Guy, C., Maynard, J., Sampson, J.R., Cheadle, J.P. Cancer Res. (2005) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
