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IL-1 family members as candidate genes modulating scrapie susceptibility in sheep: localization, partial characterization, and expression

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Abstract

Scrapie (SC) is a transmissible spongiform encephalopathy (TSE) in sheep and goats. Susceptibility to this neurodegenerative disease is controlled mainly by point mutations at the PRNP locus. Other genes, apart from PRNP, have been reported to modulate resistance/susceptibility to SC. On the basis of several studies on Alzheimer’s disease and different TSE models, and of requirement for correct homeostasis of cytokines in brain, IL1B and IL1RN were chosen as putative positional and functional candidate genes that might be involved in the polygenic variance mentioned above. In the present work, ovine IL1B and IL1RN genes were partially isolated and characterized, including promoter and other regulatory regions. In addition, several sequence polymorphisms were identified. Furthermore, their cytogenetic positions on sheep chromosomes were determined by FISH and confirmed by linkage analysis, localizing both genes in OAR3p22, a region previously described as carrying a QTL for SC incubation period in sheep. Finally, expression analyses were carried out in eight naturally SC-infected and five uninfected sheep with the same genotype for PRNP (ARQ/ARQ). This comparison was performed using real-time RT-PCR in samples of spleen and cerebellum. Results showed differences in the expression of both cytokines in cerebellum (p < 0.05) but not in spleen (p > 0.05).

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Acknowledgments

The authors thank the CERSYRA-Valdepeñas and AGRAMA breeders associations, CSIC-León, CITA-Aragón, and INIA-Madrid for kindly providing the Manchega, Awassi, Assaf, Rasa Aragonesa, and Mouflon samples. They are also very grateful to Dr. E.P. Cribiu for allowing them to perform the cytogenetic mapping in his laboratory and to Dr. K.G. Dodds for his suggestions and editing of the manuscript for English grammar.

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Authors and Affiliations

  1. Departamento de Mejora Genética Animal, INIA, Ctra La Coruña Km 7.5, 28040, Madrid, Spain

    Ane Marcos-Carcavilla, Carmen González, Estefânia Alves & Magdalena Serrano

  2. Unidad de Tecnología en Producción Animal, Avda. Montañana 930, CITA, 50059, Zaragoza, Spain

    Jorge H. Calvo

  3. Laboratoire de Génétique biochimique et de Cytogénétique, Département de Génétique Animale, INRA, Centre de Recherche de Jouy, 78352, Jouy-en-Josas, Cedex, France

    Katayoun Moazami-Goudarzi, Pascal Laurent, Maud Bertaud & Hélène Hayes

  4. AgResearch, Invermay Agricultural Centre, Private Bag, 50034, Mosgiel, New Zealand

    Anne E. Beattie

  5. Laboratorio de Genética Bioquímica, Facultad de Veterinaria, Universidad de Zaragoza, Miguel Server 177, 50013, Zaragoza, Spain

    Carmen Serrano, Jaber Lyahyai, Inmaculada Martín-Burriel & Pilar Zaragoza

  6. Centro Nacional de Referencia de EETs, Universidad de Zaragoza, Miguel Server 177, 50013, Zaragoza, Spain

    Juan J. Badiola

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  1. Ane Marcos-Carcavilla
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Correspondence to Ane Marcos-Carcavilla.

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Marcos-Carcavilla, A., Calvo, J.H., González, C. et al. IL-1 family members as candidate genes modulating scrapie susceptibility in sheep: localization, partial characterization, and expression. Mamm Genome 18, 53–63 (2007). https://doi.org/10.1007/s00335-006-0095-6

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