Dr. med. Nicolina Südkamp (Bochum / DE), Prof. Dr. Kristina Lorenz (Dortmund / DE; Würzburg / DE), Dr. Andreas Hentschel (Dortmund / DE), PD Dr.rer nat Andreas Roos (Bochum / DE), Marlena Rohm (Bochum / DE), Prof. Dr. Matthias Vorgerd (Bochum / DE)
Abstract-Text (inkl. Referenzen)
Calpainopathy (LGMDR1) is the most common limb girdle muscular dystrophy (LGMD) worldwide without a causal treatment available. To further investigate potential medical treatment a well described animal model is required. The aim of this study is a detailed characterization of the clinical course of calpainopathy in a calpain3 (CAPN3)-deficient mouse model (129S4/SvJaeJ-Capn3em5Lutzy/J) and to describe correlations between motor symptoms, histopathological changes, and biochemical properties.
To define the phenotype of this mouse model, four mutant and control mice are housed in the IntelliCage system for one week every two months until they reach an age of 15 months. This Cage allows to continuously analyze weight, drinking behavior and running wheel activity without human interactions. At same timepoints, motor function is analyzed by wire hang test, beam walk and grip strength. Additionally, further investigation of muscle tissue is conducted. CAPN3 protein expression is quantified by immunofluorescent staining and western blot. Expression of CAPN3 mRNA is quantified via rtPCR. In addition, proteomic studies and staining of muscles are performed to define dystrophic features in the course of the disease.
We will present behavioral, histopathological, and biochemical data of a CAPN3-deficient mouse model. This will serve as a base for future studies concerning innovative treatment of LGMDR1, e.g. gene therapy, and for comparisons with data from human LGMDR1 patients.