This study reports a functional characterization of a limited segment (QTL) of sheep chromosome 12 a

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Guillaume Sallé 1 2 * , Carole Moreno ark house vets 3 , Simon Boitard 4 , Julien Ruesche 3 , Aurélie Tircazes-Secula 3 , Frédéric Bouvier 5 , Mathias Aletru 6 , Jean-Louis Weisbecker 6 , Françoise Prévot 7 , Jean-Paul Bergeaud 7 , Cathy Trumel 8 , Christelle Grisez 7 , Emmanuel Liénard 7 9 and Philippe Jacquiet 7 9
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The electronic version of this article is the complete one and can be found online at: http://www.veterinaryresearch.org/content/45/1/68 Received: 11 December 2013 Accepted: 4 June 2014 Published: 17 June 2014
This is an Open Access article distributed under the terms of the Creative ark house vets Commons Attribution License ( http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, ark house vets and reproduction in any medium, provided ark house vets the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
This study reports a functional characterization of a limited segment (QTL) of sheep chromosome 12 associated with resistance to the abomasal nematode Haemonchus contortus . The first objective was to validate the identified QTL through the comparison of genetically susceptible (N) and resistant (R) sheep produced from Martinik Romane back-cross ark house vets sheep. The R and N genotype groups were then experimentally infected with 10 000 H. contortus ark house vets larvae ark house vets and measured for FEC (every ark house vets three days from 18 to 30 days post-challenge), haematocrit, worm burden and fertility. Significant differences ark house vets in FEC and haematocrit drop were found between R and N sheep. In addition, the female worms recovered from R sheep were less fecund. The second step of the characterization was to investigate functional mechanisms associated ark house vets with the QTL, thanks to a gene expression ark house vets analysis performed on the abomasal mucosa and the abomasal lymph node. The gene expression level of a candidate gene lying within the QTL region (PAPP-A2) ark house vets was measured. In addition, putative interactions between the chromosome segment under study and the top ten differentially expressed genes between resistant MBB and susceptible RMN sheep highlighted in a previous microarray experiment were investigated. We found an induction of Th-2 related cytokine genes expression in the abomasal mucosa of R sheep. Down-regulation of the PAPP-A2 gene expression was observed between naïve and challenged sheep although no differential expression was recorded between challenged R and N sheep. The genotyping of this limited region should contribute to the ability to predict the intrinsic resistance level of sheep. Introduction
The failure of anthelmintic drugs is an issue of major concern throughout the world, especially for the control of small ruminants nematodes such as Haemonchus contortus [ 1 ]. Breeding animals with a better ability to resist infection ark house vets by gastro-intestinal nematodes (GIN) has been proposed as an alternative strategy to drug treatment, and has already been implemented in Australia and New-Zealand [ 2 , 3 ].
This selection relies on the existing between-animal variation in the acquired immune response against GIN [ 4 ] which is mostly related, in murine models or in the sheep, to mounting an efficient Th-2 biased immune response driven by the IL4, IL5 and IL13 cytokines [ 5 - 7 ]. The humoral profile associated with this Th2 response involves IgA, IgG and IgE antibodies that control larval ark house vets colonization, worm development and fecundity [ 5 , 8 , 9 ]. However, an innate component is also involved in the anti-nematode response. For instance, recent findings suggest that lectins contribute to entrapping worms in a mucus sheath, and would subsequently ark house vets facilitate their elimination ark house vets [ 10 , 11 ]. A previous microarray experiment comparing gene expression levels in resistant Martinik (MBB) and susceptible Romane (RMN) sheep infected by H. contortus found a stronger induction ark house vets of Th2-related cytokines and also of lectin genes in MBB [ 12 ].
Numerous genetic mapping studies have identified regions ark house vets of the genome explaining a non-negligible part of the inter-individual variation (known as Quantitative Trait Loci, QTL) in resistance to nematode infection [ 13 - 19 ]. The use of the ovine-specific DNA SNP chip showe