Human and rat renal proximal tubule in vitro models for ADME applications.

The kidney is a major organ dictating excretion rates of chemicals and their metabolites from the body and thus renal clearance is frequently a major component of pharmaco-(toxico)-kinetic profiles. Within the nephron, the proximal tubule is the major site for xenobiotic reabsorption from glomerular filtrate and xenobiotic secretion from the blood into the lumen via the expression of multiple inward (lumen to interstitium) and outward transport systems (interstitium to lumen). While there exist several human proximal tubular cell culture options that could be utilized for modelling the proximal tubule component of renal clearance, they do not necessarily represent the full complement of xenobiotic transport processes of their in vivo counterparts.

High-yield identification of pathogenic NF1 variants by skin fibroblast transcriptome screening after apparently normal diagnostic DNA testing.

Neurofibromatosis type 1 (NF1) is caused by inactivating mutations in NF1. Due to the size, complexity, and high mutation rate at the NF1 locus, the identification of causative variants can be challenging. To obtain a molecular diagnosis in 15 individuals meeting diagnostic criteria for NF1, we performed transcriptome analysis (RNA-seq) on RNA obtained from cultured skin fibroblasts.