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Open Access Research article

Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

Camilla S Bruun1, Claus B Jørgensen1, Lene Bay1, Susanna Cirera1, Henrik E Jensen2, Páll S Leifsson2, Jens Nielsen3, Knud Christensen1 and Merete Fredholm1*

Author Affiliations

1 Department of Basic Animal and Veterinary Sciences, Faculty of Life Sciences, University of Copenhagen, Grønnegårdsvej 3, DK-1870 Frederiksberg, Denmark

2 Department of Veterinary Pathobiology, Faculty of Life Sciences, University of Copenhagen, Ridebanevej 3, DK-1870 Frederiksberg, Denmark

3 National Veterinary Institute, Technical University of Denmark, Lindholm, DK-4771 Kalvehave, Denmark

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BMC Genomics 2008, 9:283  doi:10.1186/1471-2164-9-283

Published: 12 June 2008

Abstract

Background

A pig phenotype characterized by juvenile hairlessness, thin skin and age dependent lung emphysema has been discovered in a Danish pig herd. The trait shows autosomal co-dominant inheritance with all three genotypes distinguishable. Since the phenotype shows resemblance to the integrin β6 -/- knockout phenotype seen in mice, the two genes encoding the two subunits of integrin αvβ6, i.e. ITGB6 and ITGAV, were considered candidate genes for this trait.

Results

The mutated pig phenotype is characterized by hairlessness until puberty, thin skin with few hair follicles and absence of musculi arrectores pili, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine ITGB6 andITGAV orthologs map to SSC15. In an experimental family (n = 113), showing segregation of the trait, the candidate region was confirmed by linkage analysis with four microsatellite markers. Mapping of the porcine ITGB6 and ITGAV in the IMpRH radiation hybrid panel confirmed the comparative mapping information. Sequencing of the ITGB6 and ITGAV coding sequences from affected and normal pigs revealed no evidence of a causative mutation, but alternative splicing of the ITGB6 pre-mRNA was detected. For both ITGB6 and ITGAV quantitative PCR revealed no significant difference in the expression levels in normal and affected animals. In a western blot, ITGB6 was detected in lung protein samples of all three genotypes. This result was supported by flow cytometric analyses which showed comparable reactions of kidney cells from affected and normal pigs with an integrin αvβ6 monoclonal antibody. Also, immunohistochemical staining of lung tissue with an integrin β6 antibody showed immunoreaction in both normal and affected pigs.

Conclusion

A phenotype resembling the integrin β6 -/- knockout phenotype seen in mice has been characterized in the pig. The candidate region on SSC15 has been confirmed by linkage analysis but molecular and functional analyses have excluded that the mutated phenotype is caused by structural mutations in or ablation of any of the two candidate genes.