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Differences in renal cortex transcriptional profiling of wild-type and novel type B cystinuria model rats

ABSTRACT: Cystinuria is a genetic disorder of cystine transport that accounts for 1–2% of all cases of renal lithiasis. It is characterized by hyperexcretion of cystine in urine and recurrent cystine lithiasis. Defective transport of cystine into epithelial cells of renal tubules occurs because of mutations of the transport heterodimer, including protein b0,+AT (encoded by SLC7A9) and rBAT (encoded by SLC3A1) linked through a covalent disulfide bond. Study generated a novel type B cystinuria rat model by artificially deleting 7bp of Slc7a9 gene exon 3 using the CRISPR-Cas9 system, and those Slc7a9-deficient rats were proved to be similar with cystinuria in terms of genome, transcriptome, translation, and biologic phenotypes and typical secondary changes as medullary fibrosis. Study then established the first transcription database of type B cystinuria based on this novel cystinuria rat model. In accordance with the functional annotation of DEGs, the potential role of glutathione metabolism processes in kidney of cystinuria rat model was proposed, and KEGG analysis results showed that knock-out of Slc7a9 gene triggered more biological changes which has not been study. This rat model and its transcriptional database that mimics the pathogenesis and clinical consequences of human type B cystinuria was generated for a better understanding of pathophysiological mechanism underlying in cystinuria that can be used to provide references when looking for new target and strategies for reducing kidney damage of cystinuria patients.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE178871 | GEO | 2021/06/26

REPOSITORIES: GEO

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