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在一个实验性攻毒模型中,CXCR1单倍型的基因变异与乳房链球菌感染的严重程度相关。

Genetic variation in CXCR1 haplotypes linked to severity of Streptococcus uberis infection in an experimental challenge model.

作者信息

Siebert Lydia, Headrick Susan, Lewis Mark, Gillespie Barbara, Young Charlie, Wojakiewicz Leszek, Kerro-Dego Oudessa, Prado Maria E, Almeida Raul, Oliver Stephen P, Pighetti Gina M

机构信息

Department of Animal Science, 2506 River Drive, Institute of Agriculture, The University of Tennessee, Knoxville, TN 37996, USA.

East Tennessee Research and Education Center, Little River Animal & Environmental Unit, 3217 Ellejoy Road, Institute of Agriculture, The University of Tennessee, Walland, TN 37886, USA.

出版信息

Vet Immunol Immunopathol. 2017 Aug;190:45-52. doi: 10.1016/j.vetimm.2017.07.005. Epub 2017 Jul 16.

Abstract

Mastitis, an inflammation of the mammary gland, costs the dairy industry billions of dollars in lost revenues annually. The prevalence and costs associated with mastitis has made genetic selection methods a target for research. Previous research has identified amino acid changes at positions 122, 207, 245, 327, and 332 in the IL8 receptor, CXCR1, that result in three dominant amino acid haplotypes: VWHKH, VWHRR, and AWQRR. We hypothesize different haplotype combinations influence a cow's resistance, strength, and duration of response to mastitis. To test this, Holstein dairy cows (n=40) were intramammarily challenged with Streptococcus uberis within 3 d post-calving. All cows developed mastitis based on isolation of S. uberis from the challenged quarter at least twice. All cows with the VWHRR x VWHRR (n=5) and AWQRR x VWHRR (n=6) haplotype combinations required antibiotic therapy due to clinical signs of mastitis and tended (P=0.08) to be different from cows with a VWHRR x VWHKH (n=6) haplotype combination where only 33.3% required antibiotic therapy. Cows with a VWHRR homozygous haplotype combination displayed significantly higher responses to challenge indicated by elevated S. uberis counts (4340±5,521.9CFU/mL; P=0.01), mammary scores (1.1±0.18; P=0.03), milk scores (0.9±0.17; P=0.002), and SCC (1,010,832±489,993cells/mL; P=0.03). Contrastingly, AWQRR x VWHRR cows had significantly lower S. uberis counts (15.3±16.46CFU/mL; P=0.01), mammary scores (0.3±0.16; P=0.03), milk scores (0±0.15; P=0.002), and SCC (239,261±92,264.3cells/mL; P=0.03). Cows of the VWHKH x VWHRR haplotype combination displayed responses to challenge statistically comparable to other haplotype combinations, but appeared to have an earlier peak in SCC in comparison to all other haplotype combinations. Haplotype combination did not influence milk yield (P=0.6). Our results suggest using combinations of the SNPs within the CXCR1 gene gives a better indication of a cow's ability to combat S. uberis mastitis and could resolve prior studies' conflicting results focusing on individual SNP.

摘要

乳腺炎是乳腺的一种炎症,每年给乳制品行业造成数十亿美元的收入损失。乳腺炎的患病率和相关成本使基因选择方法成为研究目标。先前的研究已经确定白细胞介素8受体CXCR1中第122、207、245、327和332位的氨基酸变化,这些变化产生了三种主要的氨基酸单倍型:VWHKH、VWHRR和AWQRR。我们假设不同的单倍型组合会影响奶牛对乳腺炎的抵抗力、反应强度和持续时间。为了验证这一点,在产犊后3天内,对40头荷斯坦奶牛进行乳房内接种乳房链球菌。根据从至少两次接种的乳腺中分离出乳房链球菌,所有奶牛都患上了乳腺炎。所有具有VWHRR×VWHRR(n = 5)和AWQRR×VWHRR(n = 6)单倍型组合的奶牛,由于乳腺炎的临床症状而需要抗生素治疗,并且与只有33.3%需要抗生素治疗的VWHRR×VWHKH(n = 6)单倍型组合的奶牛相比,有差异倾向(P = 0.08)。具有VWHRR纯合单倍型组合的奶牛对感染的反应明显更高,表现为乳房链球菌计数升高(4340±5521.9CFU/mL;P = 0.01)、乳腺评分(1.1±0.18;P = 0.03)、牛奶评分(0.9±0.17;P = 0.002)和体细胞计数(1010832±489993个细胞/mL;P = 0.03)。相比之下,AWQRR×VWHRR奶牛的乳房链球菌计数(15.3±16.46CFU/mL;P = 0.01)、乳腺评分(0.3±0.16;P = 0.03)、牛奶评分(0±0.15;P = 0.002)和体细胞计数(239261±92264.3个细胞/mL;P = 0.03)明显更低。VWHKH×VWHRR单倍型组合的奶牛对感染的反应在统计学上与其他单倍型组合相当,但与所有其他单倍型组合相比,体细胞计数似乎有一个更早的峰值。单倍型组合不影响产奶量(P = 0.6)。我们的结果表明,使用CXCR1基因内的单核苷酸多态性组合能更好地表明奶牛抵抗乳房链球菌性乳腺炎的能力,并可以解决先前研究中关注单个单核苷酸多态性的相互矛盾的结果。

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