Recent advances in genome editing technologies have enabled the rapid and precise manipulation of genomes, including the targeted introduction, alteration, and removal of genomic sequences. However, respective methods have been described mainly in non-differentiated or haploid cell types. Genome editing of well-differentiated renal epithelial cells has been hampered by a range of technological issues, including optimal design, efficient expression of multiple genome editing constructs, attainable mutation rates, and best screening strategies. Here, we present an easily implementable workflow for the rapid generation of targeted heterozygous and homozygous genomic sequence alterations in renal cells using transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeat (CRISPR) system. We demonstrate the versatility of established protocols by generating novel cellular models for studying autosomal dominant polycystic kidney disease (ADPKD). Furthermore, we show that cell culture-validated genetic modifications can be readily applied to mouse embryonic stem cells (mESCs) for the generation of corresponding mouse models. The described procedure for efficient genome editing can be applied to any cell type to study physiological and pathophysiological functions in the context of precisely engineered genotypes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00424-016-1924-4) contains supplementary material, which is available to authorized users.

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Zusammenfassung. Schmerzen im Handgelenk sind ein Problem, das Betroffene in ihren alltäglichen Aktivitäten deutlich einschränken kann. Die Ursachen sind mannigfaltig und die Behandlung häufig anspruchsvoll. Bei der Aufarbeitung der korrekten Diagnose ist ein systematischer Ansatz daher hilfreich. Ziel dieses Artikels ist, einen klaren Ansatz für die Evaluation von Handgelenkschmerzen bei Erwachsenen aufzuzeigen.

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The authors present a rare case of a 61-year-old patient with a metal foreign body inside the ulnar nerve in the Guyon's canal. After the surgical removal the motor function was not impaired. At 6-month follow up from the surgical removal, the patient showed a complete motor and sensory function.