Fragile X syndrome (FXS) is a neurodevelopmental disorder that is caused by mutations in the FMR1 gene. Neuroanatomical alterations have been reported in both male and female individuals with FXS, yet the morphological underpinnings of these alterations have not been elucidated. In the current study, we found structural changes in both male and female rats that model FXS, some of which are similarly impaired in both sexes, including the superior colliculus and periaqueductal gray, and others that show sex-specific changes. The splenium of the corpus callosum, for example, was only impaired in males. We also found reduced axonal caliber in the splenium, offering a mechanism for its structural changes. Furthermore, we found that overall, male rats have higher brain-wide diffusion than female rats. Our results provide insight into which brain regions are vulnerable to a loss of Fmr1 expression and reveal an impairment at the level of the axon that could cause structural changes in white matter regions.

脆性 X 综合征 (FXS) 是一种由FMR1突变引起的神经发育障碍基因。已经报道了患有 FXS 的男性和女性个体的神经解剖学改变，但这些改变的形态学基础尚未阐明。在目前的研究中，我们发现了模拟 FXS 的雄性和雌性大鼠的结构变化，其中一些在两性中同样受损，包括上丘和导水管周围灰质，还有一些表现出性别特异性变化。例如，胼胝体压部仅在男性中受损。我们还发现压部的轴突口径减小，为其结构变化提供了一种机制。此外，我们发现总体而言，雄性大鼠的全脑扩散高于雌性大鼠。我们的结果提供了对哪些大脑区域易受 Fmr1 缺失影响的洞察表达并揭示轴突水平的损伤，这可能导致白质区域的结构变化。