Heterogeneous expression of hydrocephalic phenotype in the hyh mice carrying a point mutation in alpha-SNAP

Batiz, LF; Paez, P; Jimenez, AJ; Rodríguez, S.; Wagner, C; Perez-Figares, JM; Rodriguez, EM

Abstract

The hyh mouse carrying a point mutation in the gene encoding for soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein alpha (α-SNAP) develops inherited hydrocephalus. The investigation was designed to study: (i) the clinical evolution of hyh mice; (ii) factors other than the α-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. © 2006 Elsevier Inc. All rights reserved.

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Título según WOS: Heterogeneous expression of hydrocephalic phenotype in the hyh mice carrying a point mutation in alpha-SNAP
Título según SCOPUS: Heterogeneous expression of hydrocephalic phenotype in the hyh mice carrying a point mutation in a-SNAP
Título de la Revista: Neurobioly of Disease
Volumen: 23
Número: 1
Editorial: Elsevier
Fecha de publicación: 2006
Página de inicio: 152
Página final: 168
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S0969996106000490
DOI:

10.1016/j.nbd.2006.02.009

Notas: ISI, SCOPUS