A novel mouse model of hemangiopericytoma due to loss of Tsc2. (14th August 2018)

• Record Type: Journal Article
• Authors: Du, Heng; Dreier, John R; Zarei, Mahsa; Wu, Chin-Lee; Bronson, Roderick W; Kwiatkowski, David J
• Is Part Of: Human molecular genetics. Volume 27:Number 24(2018:Dec. 15)
• Page Start: 4169
• Page End: 4175
• Publication Date: 2018-08-14
• Subjects: Human molecular genetics -- Periodicals; Human chromosome abnormalities -- Periodicals; 572.8
• DOI: 10.1093/hmg/ddy289
• Languages: English
• ISSNs: 0964-6906

Abstract

Abstract: Hemangiopericytoma (HPC) is a rare vascular tumor, which is thought to originate from pericytes. However, no direct evidence for the cell of origin has been found, and the mechanism of HPC tumorigenesis is poorly understood. Here we report that loss of the tumor suppressor gene Tsc2 in pericytes using a FoxD1 promoter driven cre allele ( Foxd1 tm1 (GFP/cre) Amc, FoxD1 GC ) leads to the formation of HPC in multiple sites. Tsc2 ff FoxD1 GC mice had stunted growth with seizures and tail and hind limb tremor with a median survival of 110 days. They also showed recombination in brain, spinal cord, tongue, liver, intestine and skeletal muscle. Distinctive perivascular tumors consisting of cells with oval nuclei and scant cytoplasm were identified in multiple sites in all Tsc2 ff FoxD1 GC mice. Immunohistochemistry staining showed a high expression of phospho-S6-S240/244, a hallmark of activated mTORC1, as well as pericyte markers NG2 and vimentin in these tumors. In summary, we demonstrate that loss of Tsc2 in pericytes generates HPC, the first mouse model of HPC reported.