The past decade has seen quantum advances in the applications of technology to biomedical sciences. Among the more remarkable achievements has been the advent of whole genome sequencing allowing complete knowledge of the genomic DNA structure of innunierable organisms and the associated molecular biologic advances enabling comprehensive manipulation of these newly discovered genomic sequences. With this has come the ability to elevate scientific investigation of kidney disease and function to refined in vivo systems in the mammalian kidney. The validation of basic scientific discoveries in kidney disease now rests with studies in genetically engineered mouse models and naturally occurring human samples. The overarching objective of the Mouse Genetics and Cell Line Core in the Yale George M. O'Brien Kidney Center is to reduce barriers and facilitate application of in vivo mouse-based technologies to the study of kidney disease and to facilitate the extension of the studies to ex vivo cell-based systems derived from engineered mutant mice.
The specific aims of the Core are to perform modification of genes of interest in bacterial artificial chromosome (BAC) for use in transgenic mice;to isolate of primary tubule ceNs and conditionally immortalized cell lines from specific nephron segments of mutant mouse strains;to facilitate generation of conditional knockout and knockin gene targeting strategies and constructs and to provide general resources for investigators in mouse genetic applications. This Core will Coordinate with the Renal Physiology and Phenotyping Core to assist investigators couple mouse genetic services with physiological studies. It will coordinate with the Human Genetics and Clinical Research to integrate new human disease gene discoveries with animal and cell line models. There is inherent synergy in the mouse model and cell line components of this Core as it allowing investigators access to the spectrum from defined in vivo models to ex vivo cell line models with identical genetic makeup. The Core now adds a novel mechanism for cell line generation based on technology developed by Core faculty, an improved BAC recombineering methodology and a new service in conditional knockout or knockin allele generation based the BAC technology.
Mouse models and cells from these mice are essential to the progress of kidney disease research. The Core serves investigators by producing mouse models and related cell lines that closely resemble human kidney diseases and provides a broad array of support services that will allow researchers to make efficient and effective use experimental use of these models:
|Lausecker, Franziska; Tian, Xuefei; Inoue, Kazunori et al. (2018) Vinculin is required to maintain glomerular barrier integrity. Kidney Int 93:643-655|
|Knauf, Felix; Velazquez, Heino; Pfann, Victoria et al. (2018) Characterization of renal NaCl and oxalate transport in Slc26a6-/- mice. Am J Physiol Renal Physiol :|
|Silva, Luciane M; Jacobs, Damon T; Allard, Bailey A et al. (2018) Inhibition of Hedgehog signaling suppresses proliferation and microcyst formation of human Autosomal Dominant Polycystic Kidney Disease cells. Sci Rep 8:4985|
|Daga, Ankana; Majmundar, Amar J; Braun, Daniela A et al. (2018) Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis. Kidney Int 93:204-213|
|Mansour, Sherry G; Hall, Isaac E; Reese, Peter P et al. (2018) Reliability of deceased-donor procurement kidney biopsy images uploaded in United Network for Organ Sharing. Clin Transplant 32:e13441|
|Manfredo Vieira, S; Hiltensperger, M; Kumar, V et al. (2018) Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science 359:1156-1161|
|Greiling, Teri M; Dehner, Carina; Chen, Xinguo et al. (2018) Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Sci Transl Med 10:|
|Nikonova, Anna S; Deneka, Alexander Y; Kiseleva, Anna A et al. (2018) Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD). FASEB J 32:2735-2746|
|van der Ven, Amelie T; Kobbe, Birgit; Kohl, Stefan et al. (2018) A homozygous missense variant in VWA2, encoding an interactor of the Fraser-complex, in a patient with vesicoureteral reflux. PLoS One 13:e0191224|
|Hao, Shoujin; Hao, Mary; Ferreri, Nicholas R (2018) Renal-Specific Silencing of TNF (Tumor Necrosis Factor) Unmasks Salt-Dependent Increases in Blood Pressure via an NKCC2A (Na+-K+-2Cl- Cotransporter Isoform A)-Dependent Mechanism. Hypertension 71:1117-1125|
Showing the most recent 10 out of 235 publications