McKinney B C, Schneider J S, Schafer G L, Lowing J L, Mohan S, Zhao M X, Heng M Y, Albin R L, Seasholtz A F, Akil H, Murphy G G
Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Genes Brain Behav. 2008 Mar;7(2):203-13. doi: 10.1111/j.1601-183X.2007.00339.x. Epub 2007 Jul 19.
Transgenic mice in which the tetracycline transactivator (tTA) is driven by the forebrain-specific calcium-calmodulin-dependent kinase II alpha promoter (CaMKII alpha-tTA mice) are used to study the molecular genetics of many behaviors. These mice can be crossed with other transgenic mice carrying a transgene of interest coupled to the tetracycline-responsive promoter element to produce mice with forebrain-specific expression of the transgene under investigation. The value of using CaMKII alpha-tTA mice to study behavior, however, is dependent on the CaMKII alpha-tTA mice themselves lacking a behavioral phenotype with respect to the behaviors being studied. Here we present data that suggest CaMKII alpha-tTA mice have a behavioral phenotype distinct from that of their wild-type (WT) littermates. Most strikingly, we find that CaMKII alpha-tTA mice, both those with a C57BL/6NTac genetic background (B6-tTA) and those with a 129S6B6F1/Tac hybrid genetic background (F1-tTA), exhibit decreased locomotor activity compared with WT littermates that could be misinterpreted as altered anxiety-like behavior. Despite this impairment, neither B6-tTA nor F1-tTA mice perform differently than their WT littermates in two commonly used learning and memory paradigms - Pavlovian fear conditioning and Morris water maze. Additionally, we find data regarding motor coordination and balance to be mixed: B6-tTA mice, but not F1-tTA mice, exhibit impaired performance on the accelerating rotarod and both perform as well as their WT littermates on the balance beam.
四环素反式激活因子（tTA）由前脑特异性钙/钙调蛋白依赖性激酶IIα启动子驱动的转基因小鼠（CaMKIIα-tTA小鼠）被用于研究多种行为的分子遗传学。这些小鼠可以与携带与四环素反应性启动子元件偶联的感兴趣转基因的其他转基因小鼠杂交，以产生在前脑特异性表达所研究转基因的小鼠。然而，使用CaMKIIα-tTA小鼠研究行为的价值取决于CaMKIIα-tTA小鼠本身在被研究行为方面缺乏行为表型。在这里，我们展示的数据表明CaMKIIα-tTA小鼠具有与其野生型（WT）同窝仔不同的行为表型。最引人注目的是，我们发现具有C57BL/6NTac遗传背景的CaMKIIα-tTA小鼠（B6-tTA）和具有129S6B6F1/Tac杂交遗传背景的CaMKIIα-tTA小鼠（F1-tTA）与WT同窝仔相比，运动活性降低，这可能被误解为焦虑样行为改变。尽管有这种损伤，但在两种常用的学习和记忆范式——巴甫洛夫恐惧条件反射和莫里斯水迷宫中，B6-tTA和F1-tTA小鼠与它们的WT同窝仔表现并无不同。此外，我们发现关于运动协调和平衡的数据好坏参半：B6-tTA小鼠在加速转棒试验中的表现受损，但F1-tTA小鼠没有，并且在平衡木试验中两者与WT同窝仔表现相当。
