SUPPLEMENTAL REQUEST ABSTRACT The overall objective of the In Vivo Models Resource (IVMR) in the UAB Childhood Cystic Kidney Disease Center (CCKDC) is to enable the research community to study mechanisms driving renal cystogenesis and to facilitate the translation of basic discoveries into clinical care for PKD patients. As indicated in the specific aims from the original application, we are accomplishing these goals through the generation and distribution of mice with PKD/ciliopathy mutations, PKD protein reporter lines, and biosensors for pathways associated with cystic kidney disorders. However, there is an additional demand for PKD patient relevant rat models based on multiple resource requests and feedback we've received from PKD investigators that participated in the PKD RRC Annual Symposium and the FASEB PKD Summer Research Conference. The generation of rat PKD models was not included in the scope of work or budget of the original proposal. Thus, the purpose of this supplement is to request funds that will allow the UAB IVMR to generate patient variant models for PKD1 and PKD2, along with conditional flox alleles. In the absence of this supplemental support, we would not be able to generate these models to fulfil the resource request from the research community. Null mutations in PKD1 and PKD2 in rats are lethal. Thus, we are proposing to generate alleles that were identified as homozygous changes in human ADPKD patients and thus are likely hypomorphic mutations. The PKD1(R3268C) and PKD2(L656W) models we are generating will be the first patient relevant lines to be established in the rat system. The floxed alleles will facilitate conditional deletion for temporal analysis of gene function and cyst formation and would be utilized in genetic crosses with the PKD1(R3268C) and PKD2(L656W) in the off chance that the hypomorphic alleles are homozygous lethal. All the new rat lines we generate will be distributed through the PKD RRC as soon as they pass quality control standards. Collectively these new models will provide expanded opportunities for preclinical drug testing, analysis of disease mechanisms, and will facilitate renal physiology studies that are exceedingly challenging using the mouse models.