Caplazi P A, O'Rourke K I, Baszler T V
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA.
J Clin Pathol. 2004 Jun;57(6):647-50. doi: 10.1136/jcp.2003.012203.
In sheep, susceptibility to scrapie, which is similar to human prion diseases such as Kuru and variant Creutzfeldt-Jakob disease (vCJD), is determined by prion protein (PrP) gene (Prnp) polymorphisms. Sheep with genotype ARQ/ARQ, denoting polymorphisms at codons 136, 154, and 171, are susceptible, whereas those with genotypes ARR/ARQ and ARR/ARR are resistant, indicating dominance of ARR over the ARQ allele.
Based on familial CJD E200K, 129V, where preferential use of the 200E allele in EK heterozygous individuals confers resistance, heterozygous ARR/ARQ sheep were used to test the hypothesis that resistance is caused by preferential use of the ARR allele.
After assessment of equivalent PrP expression across genotypes, allele use was analysed by sequencing reverse transcription polymerase chain reaction derived DNA clones containing the Prnp gene coding sequence.
The ARR to ARQ ratio was 1.1 in 133 clones, representing Prnp mRNA from three ARR/ARQ sheep, indicating equal use of both alleles.
Dominance of the resistant associated allele in sheep scrapie involves mechanisms other than the absence of PrP derived from the disease associated ARQ allele.
在绵羊中，对痒病的易感性类似于人类朊病毒疾病，如库鲁病和变异型克雅氏病（vCJD），由朊病毒蛋白（PrP）基因（Prnp）多态性决定。基因型为ARQ/ARQ的绵羊，即在密码子136、154和171处存在多态性，是易感的，而基因型为ARR/ARQ和ARR/ARR的绵羊是抗性的，这表明ARR对ARQ等位基因具有显性。
基于家族性克雅氏病E200K、129V，其中EK杂合个体中200E等位基因的优先使用赋予抗性，使用杂合ARR/ARQ绵羊来检验抗性是由ARR等位基因的优先使用引起的这一假设。
在评估各基因型间等效的PrP表达后，通过对包含Prnp基因编码序列的逆转录聚合酶链反应衍生的DNA克隆进行测序来分析等位基因的使用情况。
在代表三只ARR/ARQ绵羊Prnp mRNA的133个克隆中，ARR与ARQ的比例为1.1，表明两个等位基因的使用情况相同。
绵羊痒病中抗性相关等位基因的显性涉及除缺乏源自疾病相关ARQ等位基因的PrP之外的其他机制。
