title: Right Ventricular Epicardial Fibrosis in Mice With Sternal Segment Dislocation.
abstract: We report coincident sternal segment dislocation and focally extensive right ventricular epicardial fibrosis observed during routine histopathology evaluation of C57BL/6N mice as part of a high throughput phenotyping screen conducted between 4 and 16 weeks of age. This retrospective case series study was conducted to determine whether cardiac fibrosis was a pathological consequence of sternal segment dislocation. We identified sternal segment dislocation in 51 of the total 1103 mice (4.6%) analyzed at 16 weeks of age. Males were more frequently affected. In all cases but 2, the dislocation occurred at the fourth intersternebral joint. In 42 of the 51 cases (82.4%), the dislocation was encased by regenerative cartilaginous callus that protruded internally into the thoracic cavity (intrathoracic callus) and/or externally to the outer aspect of the sternum (extrathoracic callus). Displacement of dislocated ends of the sternum into the thoracic cavity was present in 19 of 51 cases (36.5%). Coincident minimal or mild right ventricular epicardial and subepicardial fibrosis was observed in 22 of the 51 cases (43%) but was not observed in any of the mice in the absence of sternal segment dislocation. Our data suggest that right ventricular fibrosis was likely caused by direct injury of the right ventricle by the dislocated ends of the sternum and/or by intrathoracic callus that develops post dislocation. Potential pathogenesis for the sternal and cardiac lesions and their implication for the interpretation of phenotypes in mouse models of cardiopulmonary and skeletal disease are discussed.
authors.affiliation: Centre for Modeling Human Disease, Toronto Centre for Phenogenomics, Toronto, ON, Canada Physiology & Experimental Medicine Research Program, The Hospital for Sick Children, Toronto, ON, Canada Department of Laboratory Medicine & Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada adissu@lunenfeld.ca.
authors.forename: H A
authors.initials: HA
authors.lastname: Adissu
authors.affiliation: Population Medicine, University of Guelph, Ontario Veterinary College, Guelph, ON, Canada.
authors.forename: G A
authors.initials: GA
authors.lastname: Medhanie
authors.affiliation: Centre for Modeling Human Disease, Toronto Centre for Phenogenomics, Toronto, ON, Canada Physiology & Experimental Medicine Research Program, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Morikawa
authors.affiliation: Mouse Genetics Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: J K
authors.initials: JK
authors.lastname: White
authors.affiliation: Centre for Modeling Human Disease, Toronto Centre for Phenogenomics, Toronto, ON, Canada Physiology & Experimental Medicine Research Program, The Hospital for Sick Children, Toronto, ON, Canada Department of Laboratory Medicine & Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Newbigging
authors.affiliation: Centre for Modeling Human Disease, Toronto Centre for Phenogenomics, Toronto, ON, Canada Physiology & Experimental Medicine Research Program, The Hospital for Sick Children, Toronto, ON, Canada Department of Laboratory Medicine & Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: C
authors.initials: C
authors.lastname: McKerlie
mesh_terms: D000818:Animals; D005260:Female; D005355:Fibrosis / Q000662:veterinary; D006352:Heart Ventricles / Q000473:pathology*; D004204:Joint Dislocations / Q000473:pathology / Q000662:veterinary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000033:anatomy & histology*; D010496:Pericardium / Q000473:pathology*; D010641:Phenotype; D012189:Retrospective Studies; D013249:Sternum / Q000293:injuries* / Q000473:pathology
keywords: callus; dislocation; epicardium; fibrosis; heart; mice; sternum