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SKP2 knockout in Rb1/p53 deficient transgenic mouse models of osteosarcoma induces macrophage infiltration and drives transcription of genes with favorable prognosis in patients

ABSTRACT: To study SKP2 in osteosarcoma, we generated a Skp2 KO line and a Skp2 intact line of transgenic OS mouse models: germline Skp2 knockout (“TKO”: Osx1-Cre;Rb1lox/lox;p53lox/lox;SKP2) versus Skp2 intact (“DKO”: Osx1-Cre;Rb1lox/lox;p53lox/lox). We then performed bulk RNAseq of the SKP2 KO vs SKP2 intact OS.

ORGANISM(S): Mus musculus

PROVIDER: GSE226634 | GEO | 2023/10/02

REPOSITORIES: GEO

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Modeling tumor subtypes in vivo using lineage restricted transgenic shRNA

Project description:Expression analysis from two genetically engineered mouse models of osteosarcoma determine the expression profile of mouse osteosarcoma Human osteosarcoma (OS) is comprised of three different subtypes: fibroblastic, chondroblastic and osteoblastic. We previously generated a mouse model of fibroblastic OS by conditional deletion of p53 and Rb in osteoblasts. Here we report an accurate mouse model of the osteoblastic subtype using shRNA-based suppression of p53. Like human OS, tumors frequently present in the long bones and preferentially disseminate to the lungs; features less consistently modeled using Cre:lox approaches. Our approach allowed direct comparison of the in vivo consequences of targeting the same genetic drivers using different technology. This demonstrated that the effects of Cre:lox and shRNA mediated knock-down are qualitatively different, at least in the context of osteosarcoma. Through the use of complementary genetic modification strategies we have established a model of a distinct clinical subtype of OS that was not previously represented and more fully recapitulated the clinical spectrum of this human tumor. 4 primary tumors from Cre:lox OS model; 4 primary tumors from shRNA OS model.

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2023-10-16 | GSE245495 | GEO

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