title: Heterozygous deletion of sarcolipin maintains normal cardiac function.
abstract: Sarcolipin (SLN) is a small proteolipid and a regulator of sarco(endo)plasmic reticulum Ca(2+)-ATPase. In heart tissue, SLN is exclusively expressed in the atrium. Previously, we inserted Cre recombinase into the endogenous SLN locus by homologous recombination and succeeded in generating SLN-Cre knockin (Sln(Cre/+)) mice. This Sln(Cre/+) mouse can be used to generate an atrium-specific gene-targeting mutant, and it is based on the Cre-loxP system. In the present study, we used adult Sln(Cre/+) mice atria and analyzed the effects of heterozygous SLN deletion by Cre knockin before use as the gene targeting mouse. Both SLN mRNA and protein levels were decreased in Sln(Cre/+) mouse atria, but there were no morphological, physiological, or molecular biological abnormalities. The properties of contractility and Ca(2+) handling were similar to wild-type (WT) mice, and expression levels of several stress markers and sarcoplasmic reticulum-related protein levels were not different between Sln(Cre/+) and WT mice. Moreover, there was no significant difference in sarco(endo)plasmic reticulum Ca(2+)-ATPase activity between the two groups. We showed that Sln(Cre/+) mice were not significantly different from WT mice in all aspects that were examined. The present study provides basic characteristics of Sln(Cre/+) mice and possibly information on the usefulness of Sln(Cre/+) mice as an atrium-specific gene-targeting model.
authors.affiliation: Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan;
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shimura
authors.affiliation: Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan;
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kusakari
authors.affiliation: Department of Biofunctional Informatics, Tokyo Medical and Dental University, Tokyo, Japan;
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Sasano
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University, Kyoto, Japan;
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakashima
authors.affiliation: Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan;
authors.forename: Gaku
authors.initials: G
authors.lastname: Nakai
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Institute of Ageing Research, School of Medicine, Hangzhou Normal University, Hangzhou, China;
authors.forename: Qibin
authors.initials: Q
authors.lastname: Jiao
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Kanagawa, Japan;
authors.forename: Meihua
authors.initials: M
authors.lastname: Jin
authors.affiliation: Departments of Anesthesiology, Physiology and Medicine, Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, California;
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yokota
authors.affiliation: Cardiovascular Research Institute, Yokohama City University, Kanagawa, Japan;
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, California; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California; and Molecular Biology Institute, University of California, Los Angeles, California.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakano
authors.affiliation: Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan;
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Goda
authors.affiliation: Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan; Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan; sminamis@jikei.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Minamisawa
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000235:genetics; D005260:Female; D005355:Fibrosis; D017353:Gene Deletion; D005838:Genotype; D006579:Heterozygote; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics*; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011510:Proteolipids / Q000172:deficiency / Q000235:genetics*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects / Q000235:genetics*
chemical_list: D000318:Adrenergic beta-Agonists; D009124:Muscle Proteins; D011510:Proteolipids; C077258:sarcolipin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D007545:Isoproterenol
keywords: Cre knockin; atrium; calcium homeostasis; sarcoplasmic reticulum