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: Luis Federico Bátiz, Patricia Páez, Antonio J Jiménez, Sara Rodríguez, Carolina Wagner, José Manuel Pérez-Fígares, Esteban Martín Rodríguez
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 23 Issue 1 Pg. 152-68 (Jul 2006) ISSN: 0969-9961 [Print] United States
• PMID: 16697210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins

Topics

• Animals
• Disease Models, Animal
• Female
• Hydrocephalus (genetics, pathology, physiopathology)
• Immunohistochemistry
• Male
• Maternal Age
• Mice
• Mice, Mutant Strains
• Microscopy, Electron, Scanning
• Parity
• Phenotype
• Point Mutation
• Pregnancy
• Sex Factors
• Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins (genetics)