title: Spontaneous cardiac calcinosis in BALB/cByJ mice.
abstract: BALB/c mice are predisposed to dystrophic cardiac calcinosis-the mineralization of cardiac tissues, especially the right ventricular epicardium. In previous reports, the disease appeared in aged animals and had an unknown etiology. In the current study, we report a substrain of BALB/c mice (BALB/cByJ) that develops disease early and with high frequency. Here we analyzed hearts grossly to identify the presence and measure the severity of disease and to compare BALB/c substrains. Histologic analysis and fluorescent and immunofluorescent microscopy were used to characterize the calcinotic lesions. BALB/cByJ mice exhibited more frequent and severe calcium deposition than did BALB/c mice of other substrains (90% compared with 3% at 5 wk). At this age, lesions covered an average of 30% of the total ventricular surface area in BALB/cByJ mice, compared with less than 1% in other strains. In bone-marrow-chimeric mice, green fluorescent protein was used as a marker to show that the lesions contain an infiltration of cells of bone marrow origin. Lesion histology showed that calcium deposits were surrounded by fibrosis with interspersed immune cells. Lymphocytes, macrophages, and granulocytes were all present. Internalization of the gap-junction protein connexin 43 was observed in myocytes adjacent to lesions. In conclusion, BALB/cByJ mice exhibit more frequent and severe dystrophic cardiac calcinosis than do other BALB/c substrains. Our findings suggest that immune cells are actively recruited to lesions and that myocyte gap junctions are altered near lesions.
authors.affiliation: Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, New York, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Glass
authors.forename: Wanda
authors.initials: W
authors.lastname: Coombs
authors.forename: Steven M
authors.initials: SM
authors.lastname: Taffet
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D009202:Cardiomyopathies / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D018031:Connexin 43 / Q000378:metabolism; D017629:Gap Junctions / Q000276:immunology / Q000473:pathology; D006098:Granulocytes / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006652:Histological Techniques / Q000662:veterinary; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence / Q000662:veterinary; D012376:Rodent Diseases / Q000276:immunology* / Q000473:pathology*; D013045:Species Specificity
chemical_list: D018031:Connexin 43; D049452:Green Fluorescent Proteins
references.citation: J Biol Chem. 2008 Mar 21;283(12):7608-15
references.pmid: 18201967
references.citation: Physiol Genomics. 2001 Aug 28;6(3):137-44
references.pmid: 11526197
references.citation: FEMS Immunol Med Microbiol. 2008 Jun;53(1):72-8
references.pmid: 18400010
references.citation: Lab Anim Sci. 1972 Jun;22(3):344-52
references.pmid: 4338698
references.citation: Curr Top Microbiol Immunol. 1985;122:19-30
references.pmid: 2994956
references.citation: Gen Physiol Biophys. 2010 Sep;29(3):222-33
references.pmid: 20817946
references.citation: Lab Anim Sci. 1975 Dec;25(6):787
references.pmid: 1207050
references.citation: J Natl Cancer Inst. 1968 Apr;40(4):683-5
references.pmid: 5646497
references.citation: Proc Natl Acad Sci U S A. 1996 May 28;93(11):5483-8
references.pmid: 8643601
references.citation: Science. 2009 Jul 31;325(5940):612-6
references.pmid: 19644120
references.citation: Am J Pathol. 2004 Apr;164(4):1379-87
references.pmid: 15039225
references.citation: Circ J. 2007 Mar;71(3):382-9
references.pmid: 17322640
references.citation: Lab Anim Sci. 1976 Apr;26(2 Pt 2):329-33
references.pmid: 1271745
references.citation: Ann Intern Med. 2000 Mar 21;132(6):444-50
references.pmid: 10733443
references.citation: Anat Rec. 1965 Jun;152(2):199-209
references.pmid: 5842161
references.citation: Cardiovasc Res. 2007 Nov 1;76(2):323-30
references.pmid: 17658501
references.citation: Heart Views. 2011 Jan;12(1):40-1
references.pmid: 21731810
references.citation: Circ Res. 2010 Apr 2;106(6):1153-63
references.pmid: 20167932
references.citation: Proc Soc Exp Biol Med. 1964 Feb;115:496-7
references.pmid: 14121647
references.citation: Circulation. 1982 Jun;65(6):1230-5
references.pmid: 6280889
references.citation: Mol Immunol. 2009 Sep;46(15):2938-46
references.pmid: 19608277
references.citation: Lab Anim Sci. 1997 Feb;47(1):11-8
references.pmid: 9051642
references.citation: Lab Anim Sci. 1983 Jun;33(3):247-8
references.pmid: 6308343
references.citation: Proc (Bayl Univ Med Cent). 2005 Jan;18(1):38-55
references.pmid: 16200146
references.citation: Calcif Tissue Int. 2009 Sep;85(3):267-75
references.pmid: 19690791
references.citation: Am J Pathol. 1986 Aug;124(2):207-15
references.pmid: 3017116
references.citation: Cardiovasc Pathol. 2011 Mar-Apr;20(2):e79-83
references.pmid: 20598909
references.citation: Curr Top Microbiol Immunol. 1985;122:1-5
references.pmid: 3899522
references.citation: Clin Radiol. 2010 Sep;65(9):685-94
references.pmid: 20696295
references.citation: Am J Pathol. 1994 Dec;145(6):1450-62
references.pmid: 7992848
references.citation: Am J Pathol. 1978 Jan;90(1):173-86
references.pmid: 145807