Ellis-van Creveld Syndrome in Grey Alpine Cattle: Morphologic, Immunophenotypic, and Molecular Characterization

Muscatello, L V; Benazzi, C; Dittmer, K E; Thompson, K G; Murgiano, Leonardo; Drögemüller, Cord; Avallone, G; Gentile, A; Edwards, J F; Piffer, C; Bolcato, M; Brunetti, B (2015). Ellis-van Creveld Syndrome in Grey Alpine Cattle: Morphologic, Immunophenotypic, and Molecular Characterization. Veterinary pathology, 52(5), pp. 957-966. American College of Veterinary Pathologists 10.1177/0300985815588610

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Murgiano, Leonardo and Drögemüller, Cord

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

0300-9858

Publisher:

American College of Veterinary Pathologists

Language:

English

Submitter:

Cord Drögemüller

Date Deposited:

24 Aug 2015 11:04

Last Modified:

25 Aug 2015 07:14

Publisher DOI:

10.1177/0300985815588610

PubMed ID:

26077781

Uncontrolled Keywords:

EVC2; Ellis–Van Creveld syndrome; bovine; chondrodysplasia; collagen X; developmental bone diseases; growth plate; immunohistochemistry; reverse transcription polymerase chain reactiondevelopmental bone diseases

BORIS DOI:

10.7892/boris.71095

URI:

https://boris.unibe.ch/id/eprint/71095

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