Novel Method of Plasmid DNA Delivery to Mouse Bladder Urothelium by Electroporation.

Genetically engineered mouse models (GEMMs) are extremely valuable in revealing novel biological insights into the initiation and progression mechanisms of human diseases such as cancer. Transgenic and conditional knockout mice have been frequently used for gene overexpression or ablation in specific tissues or cell types in vivo. However, generating germline mouse models can be time-consuming and costly. Recent advancements in gene editing technologies and the feasibility of delivering DNA plasmids by viral infection have enabled rapid generation of non-germline autochthonous mouse cancer models for several organs. The bladder is an organ that has been difficult for viral vectors to access, due to the presence of a glycosaminoglycan layer covering the urothelium. Here, we describe a novel method developed in lab for efficient delivery of DNA plasmids into the mouse bladder urothelium in vivo. Through intravesical instillation of pCAG-GFP DNA plasmid and electroporation of surgically exposed bladder, we show that the DNA plasmid can be delivered specifically into the bladder urothelial cells for transient expression. Our method provides a fast and convenient way for overexpression and knockdown of genes in the mouse bladder, and can be applied to building GEMMs of bladder cancer and other urological diseases

Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12

Results: In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p 5 7.12 3 10-11) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p 5 0.695).Conclusion: Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage.Methods: Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 case

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

Value-added activity and co-operative development

Non-Peer Reviewe