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

Luis Federico Batiz, Patricia Páez, Antonio J. Jiménez, Sara Rodríguez, Carolina Wagner, José Manuel Pérez-Fígares, Esteban Martín Rodríguez

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30 Scopus citations

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.

Original languageEnglish
Pages (from-to)152-168
Number of pages17
JournalNeurobiology of Disease
Volume23
Issue number1
DOIs
StatePublished - Jul 2006
Externally publishedYes

Bibliographical note

Funding Information:
This study was financially supported by Grants Fondecyt 1030265, Chile to EMR, DID-2005-12, Universidad Austral de Chile to LFB, and from FIS-PI 030756, Red CIEN-Instituto de Salud Carlos III and Servicio Andaluz de Salud, Spain to JMP-F. The authors are grateful to Mr. Genaro Alvial and Mr. Ricardo Silva, from Instituto de Histología y Patología, Valdivia, Chile for valuable technical support; and Mr. Luis E. Castañeda for assistance in statistical analysis. The cooperation of Mr. César Toledo and Mr. Miguel Pineda in animal maintenance and breeding is acknowledged.

Keywords

  • α-SNAP mutation
  • Heterogeneous expression of phenotype
  • hyh mice
  • Inherited hydrocephalus
  • Long-term hydrocephalus
  • Spontaneous ventriculostomies

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