Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu Campus, Huimin Road #211, Wenjiang, 611130, Sichuan, China.
Mol Cell Biochem. 2018 Dec;449(1-2):127-136. doi: 10.1007/s11010-018-3349-1. Epub 2018 Apr 10.
Liver kinase B1 (LKB1, also called STK11) encodes a serine/threonine kinase mutated in Peutz-Jeghers cancer syndrome characterized by gastrointestinal polyposis. Although LKB1 plays an important role in regulating energy homeostasis, cell growth, and metabolism via activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), nothing is known about its molecular characteristics and possible involvement in non-specific digestive disorder (NSDD) of rabbits. In the present study, we first cloned the coding sequence (CDS) of rabbit LKB1, which consisted of 1317 bp encoding 438 amino acids (AAs) and contained a highly conserved S_TKc kinase domain. Its deduced AA sequence showed 87.93-91.10% similarities with that of other species. In order to determine its involvement in NSDD, a NSDD rabbit model was built by a dietary fiber deficiency. The polymorphic site of LKB1 was then investigated in both healthy and NSDD groups using directing sequencing. Our results suggested that a synonymous variant site (840 c. G > C, CCC→CCG) existed in its S_TKc domain, which was associated with susceptibility to NSDD. Furthermore, qPCR was utilized to examine the mRNA levels of LKB1 and its downstream targets (i.e., PRKAA2, mTOR and NF-kβ) in several intestinal-related tissues from both healthy and NSDD groups. Significant changes in their expression levels between two groups indicated that impaired LKB1 signaling contributed to the intestinal abnormality in NSDD rabbits. Taken together, it could be concluded that LKB1 might be a potential candidate gene affecting the occurrence of rabbit NSDD. This information may serve as a basis for further investigations on rabbit digestive diseases.
肝激酶 B1（LKB1，也称为 STK11）编码一种丝氨酸/苏氨酸激酶，在以胃肠道息肉为特征的 Peutz-Jeghers 癌症综合征中发生突变。虽然 LKB1 通过激活单磷酸腺苷（AMP）激活的蛋白激酶（AMPK）在调节能量稳态、细胞生长和代谢方面发挥着重要作用，但对于其分子特征及其在兔子非特异性消化紊乱（NSDD）中的可能参与作用尚不清楚。在本研究中，我们首先克隆了兔 LKB1 的编码序列（CDS），其包含 1317bp 编码 438 个氨基酸（AAs），并含有高度保守的 S_TKc 激酶结构域。其推导的 AA 序列与其他物种的相似性为 87.93-91.10%。为了确定其在 NSDD 中的参与作用，通过膳食纤维缺乏建立了 NSDD 兔模型。然后使用定向测序在健康和 NSDD 组中研究 LKB1 的多态性位点。我们的结果表明，其 S_TKc 结构域存在同义变异位点（840 c. G > C，CCC→CCG），与 NSDD 的易感性相关。此外，qPCR 用于检测健康和 NSDD 组的几个肠道相关组织中 LKB1 及其下游靶标（即 PRKAA2、mTOR 和 NF-kβ）的 mRNA 水平。两组之间其表达水平的显著变化表明，LKB1 信号的受损导致 NSDD 兔子的肠道异常。总之，可以得出结论，LKB1 可能是影响兔子 NSDD 发生的潜在候选基因。这些信息可以为进一步研究兔子消化疾病提供基础。
