Abstract
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 sheep. The R and N genotype groups were then experimentally infected with 10 000 H. contortus larvae and measured for FEC (every three days from 18 to 30 days post-challenge), haematocrit, worm burden and fertility. Significant differences 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 with the QTL, thanks to a gene expression 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) 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.
Highlights
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]
The 4-SNP-based clustering of the BCxBC sheep allowed prediction of true “high-” and “low-Faecal Egg Count (FEC)” sheep, as illustrated by the 601 eggs/g and 11546 eggs/g difference obtained between the R and N groups at 18 and 30 dpi (p = 0.02 and 0.01 respectively in both cases, Table 3)
Female H. contortus collected from R sheep were 1.6 mm shorter on average (p = 0.0013) and showed 1.5 times fewer eggs in utero (p = 5.10−4) than those recovered in N sheep (525 and 358 eggs in utero/female for the N and R groups respectively, Table 3)
Summary
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 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 [5,6,7]. Identifying the mutations controlling ovine resistance to H. contortus should improve the ability to perform genetic selection by directly targeting the genes of interest through marker-assisted selection
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