IHSFC Voucher YR 4: Development of tissue specific lncRNA MALA Tl and AhR double null mouse models for analysis of toxic responses to environmental chemicals

Abstract

Project description: To investigate the function of the MALAT1 in ? cells and to study the effects of PCB126 on the b cell population in the absence of MALAT1 in vivo, we will utilize the service of the core to establish conditional MALAT1 knockout mouse model by CRISPR/Cas9 technology in murine embryonic stem (ES) cells. The complete 6,982 bp long Malat1 sequence will be deleted, including 250 nucleotides upstream of the transcriptional start site and 321 nucleotides following the 3?-end of the Malat1 transcript. A schematic presentation of the targeted Malat1 locus, its construction by in ES cells as well as Cre- and FloxP-mediated deletions in mice are shown in the Figure. Verification of correct MALAT1 targeting in ES cells and mice will be performed by PCR and Southern Blot analysis The floxP mice once generated will then be bred with the ins1-Cre mouse to produce the pancreatic ? cell specific null mice for further investigation for the toxic responses to dosing of PCB126.