PDF(Pubmed)
Abstract：
GABAergic interneurons, including somatostatin (SST) and vasoactive intestinal peptide (VIP) positive cells, play a crucial role in cortical circuit processing. Cre recombinase-mediated manipulation of these interneurons is facilitated by commercially available knock-in mouse strains such as Sst-IRES-Cre (Sst-Cre) and Vip-IRES-Cre (Vip-Cre). However, these strains are troublesome for hearing research because they are only available on the C57BL/6 genetic background, which suffer from early onset age-related hearing loss (AHL) due to a mutation of the Cdh23 gene. To overcome this limitation, we backcrossed Sst-Cre and Vip-Cre mice to CBA mice to create normal-hearing offspring with the desired Cre transgenes. We confirmed that in these \"CBA Cre\" lines, Cre drives appropriate expression of Cre-dependent genes, by crossing CBA Cre mice to Ai14 reporter mice. To assess the hearing capabilities of the CBA Cre mice, we measured auditory brainstem responses (ABRs) using clicks and tones. CBA Cre mice showed significantly lower ABR thresholds compared to C57 control mice at 3, 6, 9, and 12 months. In conclusion, our study successfully generated Sst-Cre and Vip-Cre mouse lines on the CBA background that will be valuable tools for investigating the roles of SST and VIP positive interneurons without the confounding effects of age-related hearing loss.
摘要：
GABA能中间神经元，包括生长抑素(SST)和血管活性肠肽(VIP)阳性细胞,在皮层电路处理中起着至关重要的作用。这些中间神经元的Cre重组酶介导的操作通过市售敲入小鼠品系如Sst-IRES-Cre(Sst-Cre)和Vip-IRES-Cre(Vip-Cre)来促进。然而,这些菌株对听力研究来说很麻烦，因为它们只能在C57BL/6遗传背景下获得，由于Cdh23基因的突变而患有早发性年龄相关性听力损失（AHL）。为了克服这个限制,我们将Sst-Cre和Vip-Cre小鼠与CBA小鼠回交，以创建具有所需Cre转基因的正常听力后代。我们确认在这些“CBACre”行中，Cre驱动Cre依赖性基因的适当表达，通过将CBACre小鼠与Ai14报告小鼠杂交。为了评估CBACre小鼠的听力能力，我们使用点击和音调测量听觉脑干反应（ABR）。与C57对照小鼠相比,在3、6、9和12个月时,CBACre小鼠显示出显著更低的ABR阈值。总之,我们的研究成功地在CBA背景下产生了Sst-Cre和Vip-Cre小鼠系,这将是研究SST和VIP阳性中间神经元的作用的有价值的工具,而没有年龄相关性听力损失的混杂效应.
