Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
Sci Rep. 2017 Aug 1;7(1):7031. doi: 10.1038/s41598-017-07322-5.
Constitutive depletion of p21-activated kinase 4 (PAK4) in the mouse causes embryonic lethality associated with heart and brain defects. Given that conventional gene depletion of PAK1 or PAK3 caused functional deficits in the mouse pancreas, while gene depletion of PAK5 or PAK6 did not, we asked if PAK4 might have a functional role in pancreas development. We therefore introduced conditional, Pdx1-Cre-mediated, pancreatic PAK4 gene depletion in the mouse, verified by loss of PAK4 protein expression in the pancreas. PAK4 knock-out (KO) mice were born at Mendelian ratios in both genders. Further, morphological and immunohistochemical examinations and quantifications indicated that exocrine, endocrine and ductal compartments retained the normal proportions and distributions upon PAK4 gene depletion. In addition, body weight records and a glucose tolerance test revealed no differences between WT and PAK4 KO mice. Together, this suggests that PAK4 is dispensable for mouse pancreas development. This will facilitate future use of our Pdx1-Cre-driven conditional PAK4 KO mouse model for testing in vivo potential functions of PAK4 in pancreatic disease models such as for pancreatitis and different pancreatic cancer forms.
在小鼠中组成性耗尽 p21 激活激酶 4（PAK4）会导致胚胎致死，伴有心脏和大脑缺陷。鉴于传统的 PAK1 或 PAK3 基因耗竭会导致小鼠胰腺的功能缺陷，而 PAK5 或 PAK6 基因耗竭不会，我们想知道 PAK4 是否在胰腺发育中具有功能作用。因此，我们在小鼠中引入了条件性、Pdx1-Cre 介导的胰腺 PAK4 基因耗竭，通过胰腺中 PAK4 蛋白表达的丧失来验证。PAK4 敲除（KO）小鼠在两性中均按孟德尔比例出生。此外，形态学和免疫组织化学检查和定量分析表明，在外分泌、内分泌和导管区室中，PAK4 基因耗竭后保留了正常的比例和分布。此外，体重记录和葡萄糖耐量试验显示 WT 和 PAK4 KO 小鼠之间没有差异。综上所述，这表明 PAK4 对于小鼠胰腺的发育不是必需的。这将促进我们使用 Pdx1-Cre 驱动的条件性 PAK4 KO 小鼠模型来测试 PAK4 在胰腺炎和不同胰腺癌形式等胰腺疾病模型中的体内潜在功能。
