Naturally occurring mutations in the canine CFTR gene.
Naturally occurring mutations in the canine CFTR gene.
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犬 CFTR 基因自然发生的突变。
DOI：
10.1152/physiolgenomics.00092.2010
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发表时间：
2010
影响因子：
4.6
通讯作者：
Ballard,StephenT
中科院分区：
文献类型：
--
作者：
Spadafora,Domenico;Hawkins,EleanorC;Murphy,KeithE;Clark,LeighAnne;Ballard,StephenT
自然发生的囊性纤维化（CF）导致CFTR基因突变尚未在任何非人类动物物种中发现。由于已知家犬会发展与人类非典型CF相关的医学病症（例如，支气管扩张症和胰腺炎），我们假设患有这些疾病的狗可能比大群体具有更高的CFTR突变表达率。使用时间温度梯度凝胶电泳（TTGE）在400只动物中筛选犬CFTR：203只诊断为胰腺炎的犬，23只诊断为支气管扩张的犬，以及174只因任何疾病而入院的犬（大型犬）。28只狗被鉴定出具有四种CFTR错义突变之一。P1281 T和P1464 H突变发生在相对不保守的残基中。R1456W类似于人类R1453W突变，其具有正常CFTR功能的约20%，并且与胰腺炎和泛细支气管炎相关。R812W破坏了调节结构域内高度保守的蛋白激酶A识别位点。我们的结论是，自然发生的CFTR突变是比较常见的家犬，可以检测TTGE。未观察到突变频率的实质性差异之间的大，胰腺炎，和支气管扩张症的狗。
Naturally occurring cystic fibrosis (CF)-causing mutations in the CFTR gene have not been identified in any nonhuman animal species. Since domestic dogs are known to develop medical conditions associated with atypical CF in humans (e.g., bronchiectasis and pancreatitis), we hypothesized that dogs with these disorders likely have a higher expression rate of CFTR mutations than the at-large population. Temporal temperature-gradient gel electrophoresis (TTGE) was used to screen canine CFTR in 400 animals: 203 dogs diagnosed with pancreatitis, 23 dogs diagnosed with bronchiectasis, and 174 dogs admitted to clinics for any illness (at-large dogs). Twenty-eight dogs were identified with one of four CFTR missense mutations. P1281T and P1464H mutations occur in relatively unconserved residues. R1456W is analogous to the human R1453W mutation, which has ∼20% of normal CFTR function and is associated with pancreatitis and panbronchiolitis. R812W disrupts a highly conserved protein kinase A recognition site within the regulatory domain. We conclude that naturally occurring CFTR mutations are relatively common in domestic dogs and can be detected with TTGE. No substantive differences in mutation frequency were observed between the at-large, pancreatitis, and bronchiectasis dogs.