biostudies-literatureStransky LAHHS | NIH | National Cancer Institutein part with Federal Funds from the National Cancer Institute, National Institutes of HealthNCI NIH HHSHHS | NIH | National Cancer Institute (NCI)e2408549121https://www.ebi.ac.uk/biostudies/studies/S-EPMC11474080biostudies-literatureUnknown121(41)CRISPR is revolutionizing the ability to do somatic gene editing in mice for the purpose of creating new cancer models. Inactivation of the <i>VHL</i> tumor suppressor gene is the signature initiating event in the most common form of kidney cancer, clear cell renal cell carcinoma (ccRCC). Such tumors are usually driven by the excessive HIF2 activity that arises when the <i>VHL</i> gene product, pVHL, is defective. Given the pressing need for a robust immunocompetent mouse model of human ccRCC, we directly injected adenovirus-associated viruses (AAVs) encoding sgRNAs against <i>VHL</i> and other known/suspected ccRCC tumor suppressor genes into the kidneys of C57BL/6 mice under conditions where Cas9 was under the control of one of two different kidney-specific promoters (<i>Cdh16</i> or <i>Proceedings of the National Academy of Sciences of the United States of AmericaToward a CRISPR-based mouse model of &lt;i&gt;Vhl&lt;/i&gt;-deficient clear cell kidney cancer: Initial experience and lessons learned.PMC11474080R35CA100068; P50CA101942;HHSN261201500001GHHSN261201500003IHHSN261201500001CHHSN261201500003CHHSN261201000031CU01 CA236489T32 CA236754R35 CA210068HHSN261201500001WP50 CA101942T32CA236754Contract No.HHSN2612015000031U01CA236489Dhandapani SChoudhari SJames AYun CBi KZhao YDifilippantonio SUnite JRamesh VVigeant SMJeon ASticco-Ivins MMorris NVan Allen EMKaelin WGKalen JDWarner ACPinheiro EMIleva LSignoretti SLinehan WMLinn DETran BSchmidt LSHe LStransky LARicketts CJKarim BParab VMorgan TTuran SPignon JCGao WfalseToward a CRISPR-based mouse model of &lt;i&gt;Vhl&lt;/i&gt;-deficient clear cell kidney cancer: Initial experience and lessons learned.CRISPR is revolutionizing the ability to do somatic gene editing in mice for the purpose of creating new cancer models. Inactivation of the <i>VHL</i> tumor suppressor gene is the signature initiating event in the most common form of kidney cancer, clear cell renal cell carcinoma (ccRCC). Such tumors are usually driven by the excessive HIF2 activity that arises when the <i>VHL</i> gene product, pVHL, is defective. Given the pressing need for a robust immunocompetent mouse model of human ccRCC, we directly injected adenovirus-associated viruses (AAVs) encoding sgRNAs against <i>VHL</i> and other known/suspected ccRCC tumor suppressor genes into the kidneys of C57BL/6 mice under conditions where Cas9 was under the control of one of two different kidney-specific promoters (<i>Cdh16</i> or <i>2024-01-01T00:00:00Z2024 Oct2026-06-02T18:39:57.74Z2026-05-27T03:07:47.215ZS-EPMC114740803936582010.1073/pnas.2408549121