Sonic hedgehog (SHH) signaling is essential for the differentiation and migration of early stem cell populations during cerebellar development. Dysregulation of SHH-signaling can result in cerebellar overgrowth and the formation of the brain tumor medulloblastoma. Treatment for medulloblastoma is extremely aggressive and patients suffer life-long side effects including behavioral deficits. Considering that other behavioral disorders including autism spectrum disorders, holoprosencephaly, and basal cell nevus syndrome are known to present with cerebellar abnormalities, it is proposed that some behavioral abnormalities could be inherent to the medulloblastoma sequalae rather than treatment. Using a haploinsufficient SHH receptor knockout mouse model (Ptch1+/-), a partner preference task was used to explore activity, social behavior and neuroanatomical changes resulting from dysregulated SHH signaling. Compared to wild-type, Ptch1+/- females displayed increased activity by traveling a greater distance in both open-field and partner preference tasks. Social behavior was also sex-specifically modified in Ptch1+/- females that interacted more with both novel and familiar animals in the partner preference task compared to same-sex wild-type controls. Haploinsufficiency of PTCH1 resulted in cerebellar overgrowth in lobules IV/V and IX of both sexes, and female-specific decreases in hippocampal size and isocortical layer thickness. Taken together, neuroanatomical changes related to deficient SHH signaling may alter social behavior.

中文翻译：

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声刺猬受体（Ptch1）的杂合突变导致小脑过度生长，并且性别特异性地改变了雌性小鼠的海马和皮质层结构，活动和社交行为。

声波刺猬（SHH）信号对于小脑发育过程中早期干细胞群体的分化和迁移至关重要。SHH信号的失调可导致小脑过度生长和脑肿瘤髓母细胞瘤的形成。髓母细胞瘤的治疗极具侵略性，患者会终身遭受包括行为缺陷在内的副作用。考虑到其他行为障碍，包括自闭症谱系障碍，全前脑畸形和基底细胞痣综合征，都已知会出现小脑异常，因此提出一些行为异常可能是髓母细胞瘤所固有的，而不是治疗方法。使用单倍型SHH受体基因敲除小鼠模型（Ptch1 +/-），使用伴侣偏好任务来探索活动，SHH信号失调导致的社会行为和神经解剖学变化。与野生型相比，Ptch1 +/-雌性通过在野外和伴侣偏好任务中走更长的距离而显示出增强的活动。与同性野生型对照相比，Ptch1 +/-雌性中的社交行为也按性别进行了修改，在伴侣偏好任务中与新颖和熟悉的动物互动更多。PTCH1的单倍剂量不足会导致小叶IV / V和IX的小脑过度生长，并且女性特异性的海马体大小和等皮质层厚度减少。综上所述，与SHH信号不足有关的神经解剖学变化可能会改变社会行为。Ptch1 +/-雌性通过在野外和伴侣偏好任务中走更长的距离而显示出更多的活动。与同性野生型对照相比，Ptch1 +/-雌性中的社交行为也按性别进行了修改，在伴侣偏好任务中与新颖和熟悉的动物互动更多。PTCH1的单倍剂量不足会导致小叶IV / V和IX的小脑过度生长，并且女性特异性的海马体大小和等皮质层厚度减少。综上所述，与SHH信号不足有关的神经解剖学变化可能会改变社会行为。Ptch1 +/-雌性通过在野外和伴侣偏好任务中走更长的距离而显示出更多的活动。与同性野生型对照相比，Ptch1 +/-雌性中的社交行为也按性别进行了修改，在伴侣偏好任务中与新颖和熟悉的动物互动更多。PTCH1的单倍剂量不足会导致小叶IV / V和IX的小脑过度生长，并且女性特异性的海马体大小和等皮质层厚度减少。综上所述，与SHH信号不足有关的神经解剖学变化可能会改变社会行为。与同性野生型对照相比，Ptch1 +/-雌性中的社交行为也按性别进行了修改，在伴侣偏好任务中与新颖和熟悉的动物互动更多。PTCH1的单倍剂量不足会导致小叶IV / V和IX的小脑过度生长，并且女性特异性的海马体大小和等皮质层厚度减少。综上所述，与SHH信号不足有关的神经解剖学变化可能会改变社会行为。与同性野生型对照相比，Ptch1 +/-雌性中的社交行为也按性别进行了修改，在伴侣偏好任务中与新颖和熟悉的动物互动更多。PTCH1的单倍剂量不足会导致小叶IV / V和IX的小脑过度生长，并且女性特异性的海马体大小和等皮质层厚度减少。综上所述，与SHH信号不足有关的神经解剖学变化可能会改变社会行为。