Afferent neurons and their mechanoreceptors provide critical sensory feedback for gait. The anatomical distribution and density of afferents and mechanoreceptors influences sensory feedback, as does mechanoreceptor function. Electrophysiological studies of hind paw skin reveal the different types of afferent responses and their receptive fields, however the anatomical distribution of mechanoreceptor endings is unknown. In addition, the role of integrin α1β1 in mechanoreceptor function is unclear, though it is expressed by keratinocytes in the stratum basale where it is likely involved in a variety of mechanotransduction pathways and ion channel functionalities. For example, it has been shown that integrin α1β1 is necessary for the function of TRPV4 that is highly expressed by afferent units. The purpose of this study therefore was to determine and compare the distribution of mechanoreceptors across the hind paw skin and the footfall patterns of itga1-null and wild type mice. The itga1-null mouse is lacking the integrin α1 subunit, which binds exclusively to the β1 subunit, thus rendering integrin α1β1 nonfunctional while leaving the numerous other pairings of the β1 subunit undisturbed. Intact hind paws were processed, serially sectioned and stained to visualize mechanoreceptors. Footfall patterns were analyzed as a first step in correlating mechanoreceptor distribution and functionality. Merkel cells and Meissner-like corpuscles were present, however Ruffini endings and Pacinian corpuscles were not observed. Meissner-like corpuscles were located exclusively in the glabrous skin of the footpads and digit tips, however Merkel cells were found throughout hairy and glabrous skin. The increased density of Merkel cells and Meissner-like corpuscles in footpads 1, 3 and Meissner-like corpuscles in footpad 4 suggests their role in anteroposterior balance, while Meissner-like corpuscle concentrations in digits 2 and 5 support their role in mediolateral balance. Finally, a larger density of Meissner-like corpuscles in footpads 3 and 4 in male itga1-null mice compared to wild type controls paves the way for future site specific single fiber in vivo recordings to provide insight into the role of integrin α1β1 in tactile mechanotransduction.

中文翻译：

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小鼠后爪皮肤机械感受器的解剖分布以及整联蛋白α1β1对脚掌迈斯纳样小球密度的影响

传入神经元及其机械感受器为步态提供关键的感觉反馈。传入和机械感受器的解剖分布和密度会影响感觉反馈，机械感受器功能也会如此。后爪皮肤的电生理学研究揭示了不同类型的传入反应及其感受野，但是机械感受器末梢的解剖学分布是未知的。此外，整合素α1β1在机械感受器功能中的作用尚不清楚，尽管它由基底层中的角质形成细胞表达，在角质化细胞中它可能参与多种机械传导途径和离子通道功能。例如，已经表明整联蛋白α1β1对于由传入单位高度表达的TRPV4的功能是必需的。因此，本研究的目的是确定并比较机械感受器在后爪皮肤上的分布以及itga1-null和野生型小鼠的脚步模式。itga1-null小鼠缺少整合素α1亚基，该整合素仅与β1亚基结合，因此使整合素α1β1失去功能，而其他许多对β1亚基的干扰均不受干扰。对完整的后爪进行处理，连续切片并染色以可视化机械感受器。分析脚步模式是关联机械感受器分布和功能的第一步。存在默克尔细胞和Meissner样小体，但未观察到Ruffini末梢和Pacinian小体。像迈斯纳一样的小球仅位于脚垫和指尖的无毛皮肤中，然而，在毛茸茸的皮肤上都发现了默克尔细胞。脚垫1、3中的默克尔细胞和Meissner样小体以及脚垫4中的Meissner样小体的密度增加表明它们在前后平衡中的作用，而位数2和5中的Meissner样小体浓度支持它们在中外侧平衡中的作用。最后，与野生型对照相比，雄性itga1-null小鼠的脚垫3和4的密垫状小球密度更高，为野生型对照铺平了道路，从而为整合素α1β1在触觉机械转导中的作用提供了见解。 。而第2位和第5位的Meissner样小球浓度则支持它们在中外侧平衡中的作用。最后，与野生型对照相比，雄性itga1-null小鼠的脚垫3和4的密垫状小球密度更高，为野生型对照铺平了道路，从而为整合素α1β1在触觉机械转导中的作用提供了见解。 。而第2位和第5位的Meissner样小球浓度支持它们在中外侧平衡中的作用。最后，与野生型对照相比，雄性itga1-null小鼠的脚垫3和4的密垫状小球密度更高，为野生型对照铺平了道路，从而为整合素α1β1在触觉机械转导中的作用提供了见解。 。