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.

Public Health Relevance

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:

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK079310-07
Application #
8734394
Study Section
Special Emphasis Panel (ZDK1-GRB-6)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
7
Fiscal Year
2014
Total Cost
$304,187
Indirect Cost
$121,492
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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
Greenberg, Jason H; Devarajan, Prasad; Thiessen-Philbrook, Heather R et al. (2018) Kidney injury biomarkers 5 years after AKI due to pediatric cardiac surgery. Pediatr Nephrol 33:1069-1077
Soomro, Irfana; Sun, Ying; Li, Zhai et al. (2018) Glutamine metabolism via glutaminase 1 in autosomal-dominant polycystic kidney disease. Nephrol Dial Transplant 33:1343-1353
Warejko, Jillian K; Tan, Weizhen; Daga, Ankana et al. (2018) Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome. Clin J Am Soc Nephrol 13:53-62
Hall, Isaac E; Parikh, Chirag R; Schröppel, Bernd et al. (2018) Procurement Biopsy Findings Versus Kidney Donor Risk Index for Predicting Renal Allograft Survival. Transplant Direct 4:e373
Luciano, Amelia K; Zhou, Wenping; Santana, Jeans M et al. (2018) CLOCK phosphorylation by AKT regulates its nuclear accumulation and circadian gene expression in peripheral tissues. J Biol Chem 293:9126-9136
Greenberg, Jason H; Kakajiwala, Aadil; Parikh, Chirag R et al. (2018) Emerging biomarkers of chronic kidney disease in children. Pediatr Nephrol 33:925-933
Cornec-Le Gall, Emilie; Olson, Rory J; Besse, Whitney et al. (2018) Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease. Am J Hum Genet 102:832-844
Greenberg, Jason H; Zappitelli, Michael; Jia, Yaqi et al. (2018) Biomarkers of AKI Progression after Pediatric Cardiac Surgery. J Am Soc Nephrol 29:1549-1556

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