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SrGAP3 knockout mice display enlarged lateral ventricles and specific cilia disturbances of ependymal cells in the third ventricle

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Abstract

In several mouse models of mental retardation, ventricular enlargements have been observed. Mutation in the SrGAP3 gene residing on chromosome 3p25 has previously been associated with intellectual disability in humans. In addition, SrGAP3 is related to Rho-GAPs signaling pathways, which play essential roles in the development and plasticity of the nervous system. About 10 % of postnatal homozygous SrGAP3-deficient mice die due to hydrocephalus, whereas the remaining mice survive into adulthood but display enlarged ventricles. We analyze the ventricular enlargement of these mice by performing a post-mortem MRI approach. We found a more than 15-fold enlargement of the lateral ventricles of homozygous SrGAP3-deficient mice. Moreover, we demonstrate that this phenotype was not accompanied by a stenosis of the aqueduct. Instead, SrGAP3 knockout mice displayed reduced densities of cilia of ependymal cells in These third ventricle compared to age-matched controls. This results indicate that the ventricular enlargement may be due to ciliopathy.

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Acknowledgments

We wish to thank Mrs Hanisch and Mr Hadlich for excellent technical assistance. The study was supported by a grant from the “Forschungsverbund Neurowissenschaften Greifswald”.

Author information

Correspondence to Oliver von Bohlen und Halbach.

Additional information

Leif Koschützke and Jonathan Bertram contributed equally to this work.

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Koschützke, L., Bertram, J., Hartmann, B. et al. SrGAP3 knockout mice display enlarged lateral ventricles and specific cilia disturbances of ependymal cells in the third ventricle. Cell Tissue Res 361, 645–650 (2015). https://doi.org/10.1007/s00441-015-2224-6

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Keywords

  • Post-mortem MRI
  • Neurodevelopmental disorder
  • Hydrocephalus
  • Ciliopathy
  • MEGAP