title: Genetic disruption of Ano5 in mice does not recapitulate human ANO5-deficient muscular dystrophy.
abstract: BACKGROUND
  Anoctamin 5 (ANO5) is a member of a conserved gene family (TMEM16), which codes for proteins predicted to have eight transmembrane domains and putative Ca(2+)-activated chloride channel (CaCC) activity. It was recently reported that mutations in this gene result in the development of limb girdle muscular dystrophy type 2L (LGMD2L), Miyoshi myopathy type 3 (MMD3), or gnathodiaphyseal dysplasia 1 (GDD1). Currently, there is a lack of animal models for the study of the physiological function of Ano5 and the disease pathology in its absence.
  
  
  RESULTS
  Here, we report the generation and characterization of the first Ano5-knockout (KO) mice. Our data demonstrate that the KO mice did not present overt skeletal or cardiac muscle pathology at rest conditions from birth up to 18 months of age. There were no significant differences in force production or force deficit following repeated eccentric contractions between wild type (WT) and KO mice. Although cardiac hypertrophy developed similarly in both KO and WT mice after daily isoproterenol (ISO, 100 mg/kg) treatment via intraperitoneal injection for 2 weeks, they were functionally indiscernible. However, microarray analysis identified the genes involved in lipid metabolism, and complement pathways were altered in the KO skeletal muscle.
  
  
  CONCLUSIONS
  Taken together, these data provide the evidence to show that genetic ablation of Ano5 in C57BL/6J mice does not cause overt pathology in skeletal and cardiac muscles, but Ano5 deficiency may lead to altered lipid metabolism and inflammation signaling.
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, Biomedical Sciences Graduate Program, Biophysics Graduate Program, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, Biomedical Sciences Graduate Program, Biophysics Graduate Program, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA.
authors.forename: Mona
authors.initials: M
authors.lastname: El Refaey
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, Biomedical Sciences Graduate Program, Biophysics Graduate Program, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, Biomedical Sciences Graduate Program, Biophysics Graduate Program, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA.
authors.forename: Lixia
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, Biomedical Sciences Graduate Program, Biophysics Graduate Program, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA.
authors.forename: Yandi
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Physiology and Cell Biology, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Floyd
authors.affiliation: Department of Physiology and Cell Biology, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA.
authors.forename: Tallib
authors.initials: T
authors.lastname: Karaze
authors.affiliation: Department of Physiology and Cell Biology, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA.
authors.forename: Paul M L
authors.initials: PM
authors.lastname: Janssen
authors.affiliation: Department of Surgery, Davis Heart and Lung Research Institute, Biomedical Sciences Graduate Program, Biophysics Graduate Program, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA.
authors.forename: Renzhi
authors.initials: R
authors.lastname: Han
keywords: Anoctamin 5; Heart; Muscular dystrophy; Skeletal muscle; TMEM16E