title: Ellis-van Creveld Syndrome in Grey Alpine Cattle: Morphologic, Immunophenotypic, and Molecular Characterization.
abstract: Ellis-van Creveld (EvC) syndrome is a human autosomal recessive disorder caused by a mutation in either the EVC or EVC2 gene, and presents with short limbs, polydactyly, and ectodermal and heart defects. The aim of this study was to understand the pathologic basis by which deletions in the EVC2 gene lead to chondrodysplastic dwarfism and to describe the morphologic, immunohistochemical, and molecular hallmarks of EvC syndrome in cattle. Five Grey Alpine calves, with a known mutation in the EVC2 gene, were autopsied. Immunohistochemistry was performed on bone using antibodies to collagen II, collagen X, sonic hedgehog, fibroblast growth factor 2, and Ki67. Reverse transcription polymerase chain reaction was performed to analyze EVC1 and EVC2 gene expression. Autopsy revealed long bones that were severely reduced in length, as well as genital and heart defects. Collagen II was detected in control calves in the resting, proliferative, and hypertrophic zones and in the primary and secondary spongiosa, with a loss of labeling in the resting zone of 2 dwarfs. Collagen X was expressed in hypertrophic zone in the controls but was absent in the EvC cases. In affected calves and controls, sonic hedgehog labeled hypertrophic chondrocytes and primary and secondary spongiosa similarly. FGF2 was expressed in chondrocytes of all growth plate zones in the control calves but was lost in most EvC cases. The Ki67 index was lower in cases compared with controls. EVC and EVC2 transcripts were detected. Our data suggest that EvC syndrome of Grey Alpine cattle is a disorder of chondrocyte differentiation, with accelerated differentiation and premature hypertrophy of chondrocytes, and could be a spontaneous model for the equivalent human disease.
authors.affiliation: DIMEVET, University of Bologna, Ozzano dell'Emilia, Bologna, Italy.
authors.forename: L V
authors.initials: LV
authors.lastname: Muscatello
authors.affiliation: DIMEVET, University of Bologna, Ozzano dell'Emilia, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Benazzi
authors.affiliation: Institute of Veterinary, Animal, and Biomedical Sciences, Massey University, Palmerston North, New Zealand K.E.Dittmer@massey.ac.nz.
authors.forename: K E
authors.initials: KE
authors.lastname: Dittmer
authors.affiliation: Institute of Veterinary, Animal, and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: K G
authors.initials: KG
authors.lastname: Thompson
authors.affiliation: Institute of Genetics, University of Bern, Bern, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Murgiano
authors.affiliation: Institute of Genetics, University of Bern, Bern, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Drögemüller
authors.affiliation: DIMEVET, University of Bologna, Ozzano dell'Emilia, Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Avallone
authors.affiliation: DIMEVET, University of Bologna, Ozzano dell'Emilia, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gentile
authors.affiliation: AUSL, Bolzano, Italy.
authors.forename: J F
authors.initials: JF
authors.lastname: Edwards
authors.affiliation: Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Piffer
authors.affiliation: DIMEVET, University of Bologna, Ozzano dell'Emilia, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bolcato
authors.affiliation: DIMEVET, University of Bologna, Ozzano dell'Emilia, Bologna, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Brunetti
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000473:pathology; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D004613:Ellis-Van Creveld Syndrome / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D005260:Female; D005796:Genes / Q000235:genetics; D008297:Male; D009154:Mutation
keywords: EVC2; Ellis–Van Creveld syndrome; bovine; chondrodysplasia; collagen X; developmental bone diseases; growth plate; immunohistochemistry; reverse transcription polymerase chain reaction