Cerebrovascular phenotype analysis in Gucy1a3 loss-of-function mice: insights into moyamoya disease susceptibility

Background: loss‑of‑function and the cerebrovascular phenotype in MMD. Methods: Intracranial arterial anatomy was assessed using 7.0T high‑resolution magnetic resonance angiography (MRA) and cerebral vascular casting. Vasoconstrictive remodeling was evaluated by calculating diameter ratios - specifically, internal carotid artery (ICA)/basilar artery (BA) and middle cerebral artery (MCA)/BA ratios. Histopathological evaluation was performed using hematoxylin and eosin (H&E) staining, elastic van Gieson (EVG) staining, and α‑smooth muscle actin (α‑SMA) immunohistochemistry to assess intracerebral macrovascular pathology. Cortical microvascular density and caliber were quantified using CD31 immunohistochemistry, while leptomeningeal vascular architecture was systematically analyzed using vascular casting, followed by skeletonization and topological analysis. Results: . Conclusion: loss‑of‑function may contribute to MMD susceptibility primarily by compromising small‑vessel integrity, necessitating additional triggers for full disease manifestation.