Genome-wide analysis of differentially expressed miRNAs and their associated regulatory networks in lenses deficient for the congenital cataract-linked tudor domain containing protein TDRD7

Mutations/deficiency of TDRD7, which encodes a tudor domain containing protein involved in post-transcriptional gene expression control, causes early-onset cataract in humans and animal models. While Tdrd7 is implicated in the control of key lens mRNAs, the impact of Tdrd7 deficiency on microRNAs (miRNAs), and how this contributes to cataracts, is undefined. Here, we address this critical knowledge-gap by investigating Tdrd7-targeted knockout (Tdrd7-/-) mice that exhibit fully penetrant juvenile cataracts. To gain global insights into miRNA profile alterations, we performed Affymetrix miRNA 3.0 microarray analysis on Tdrd7-/- mouse lenses at postnatal day (P) 4, because this stage precedes cataract formation and thus informs on early miRNA misexpression while minimizing detection of secondary changes. miRNA microarray comparision of lenses fromTdrd7 targeted germline knockout (KO) mouse line (Tdrd7tm1.1Chum, or Tdrd7-/-), and wild-type control