title: Heterogeneous expression of hydrocephalic phenotype in the hyh mice carrying a point mutation in alpha-SNAP.
abstract: 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.
authors.affiliation: Instituto de Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Casilla (P.O. Box) 567, Valdivia, Chile.
authors.forename: Luis Federico
authors.initials: LF
authors.lastname: Bátiz
authors.forename: Patricia
authors.initials: P
authors.lastname: Páez
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Jiménez
authors.forename: Sara
authors.initials: S
authors.lastname: Rodríguez
authors.forename: Carolina
authors.initials: C
authors.lastname: Wagner
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Pérez-Fígares
authors.forename: Esteban Martín
authors.initials: EM
authors.lastname: Rodríguez
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006849:Hydrocephalus / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008423:Maternal Age; D051379:Mice; D008817:Mice, Mutant Strains; D008855:Microscopy, Electron, Scanning; D010298:Parity; D010641:Phenotype; D017354:Point Mutation; D011247:Pregnancy; D012737:Sex Factors; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / Q000235:genetics*
chemical_list: D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins