Bátiz Luis Federico, Páez Patricia, Jiménez Antonio J, Rodríguez Sara, Wagner Carolina, Pérez-Fígares José Manuel, Rodríguez Esteban Martín
Instituto de Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Casilla (P.O. Box) 567, Valdivia, Chile.
Neurobiol Dis. 2006 Jul;23(1):152-68. doi: 10.1016/j.nbd.2006.02.009. Epub 2006 May 11.
The hyh mouse carrying a point mutation in the gene encoding for soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein alpha (alpha-SNAP) develops inherited hydrocephalus. The investigation was designed to study: (i) the clinical evolution of hyh mice; (ii) factors other than the alpha-SNAP mutation that may influence the expression of hydrocephalus; (iii) the neuropathological features underlying the different forms of clinical evolution. The study included 3017 mice, 22.4% of which were hydrocephalic. The neuropathological study was performed in 112 mice by use of light and electron microscopy. It was found that maternal- and sex-related factors are involved in the heterogeneous expression of hyh phenotype. The clinical evolution recorded throughout a 4-year period also revealed a heterogeneous expression of the hydrocephalic phenotype. Two subpopulations were distinguished: (i) 70% of mice underwent a rapidly progressive hydrocephalus and died during the first 2 months of life; they presented macrocephaly, extremely large expansion of the ventricles, equilibrium impairment and decreased motor activity. (ii) Mice with slowly progressive hydrocephalus (30%) survived for periods ranging between 2 months and 2 years. They had no or moderate macrocephaly; moderate ventricular dilatation and preserved general motor activity; they all presented spontaneous ventriculostomies communicating the ventricles with the subarachnoid space, indicating that such communications play a key role in the long survival of these mice. The hyh mutant represents an ideal animal model to investigate how do the brain "adapt" to a virtually life-lasting hydrocephalus.
携带可溶性N - 乙基马来酰亚胺敏感因子（NSF）附着蛋白α（α - SNAP）编码基因点突变的hyh小鼠会发生遗传性脑积水。本研究旨在：（i）研究hyh小鼠的临床演变；（ii）研究除α - SNAP突变外可能影响脑积水表达的因素；（iii）研究不同临床演变形式背后的神经病理学特征。该研究包括3017只小鼠，其中22.4%患有脑积水。对112只小鼠进行了光镜和电镜下的神经病理学研究。发现母体和性别相关因素参与了hyh表型的异质性表达。在4年期间记录的临床演变也显示了脑积水表型的异质性表达。区分出两个亚群：（i）70%的小鼠发生快速进行性脑积水并在出生后的头2个月内死亡；它们表现为巨头症、脑室极度扩张、平衡受损和运动活动减少。（ii）脑积水进展缓慢的小鼠（30%）存活时间为2个月至2年。它们没有或仅有中度巨头症；脑室中度扩张且一般运动活动保留；它们都出现了使脑室与蛛网膜下腔相通的自发性脑室造口术，表明这种相通在这些小鼠的长期存活中起关键作用。hyh突变体是研究大脑如何“适应”几乎持续一生的脑积水的理想动物模型。
