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Strain differences of cerebral ventricles in mice: can the MRL/MpJ mouse be a model for hydrocephalus?
Keisuke Hino1, Saori Otsuka, Osamu Ichii
1Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Insights
MRL/MpJ mice exhibit significantly larger cerebral ventricles compared to other strains, suggesting their potential as a new animal model for studying hydrocephalus. Further research into ependymal cell function may elucidate disease mechanisms.
Area of Science:
- Neuroscience
- Comparative Anatomy
- Animal Models
Background:
- Hydrocephalus is a complex neurological condition marked by excessive cerebrospinal fluid (CSF) accumulation in the brain's ventricles.
- The precise causes and developmental mechanisms of hydrocephalus remain incompletely understood in both human and animal subjects.
- Existing animal models may not fully capture the diverse pathologies observed in human hydrocephalus.
Purpose of the Study:
- To investigate variations in cerebral ventricular morphology across five distinct inbred mouse strains.
- To evaluate the potential of MRL/MpJ mice as a novel animal model for hydrocephalus research.
- To identify potential cellular mechanisms contributing to ventricular enlargement in susceptible mouse strains.
Main Methods:
- Histological examination of cerebral ventricles in five inbred mouse strains (MRL/MpJ, C57BL/6, C3H/He, DBA/2, BALB/c).
- Quantitative analysis of ventricular volume and surface area.
- Comparative assessment of ependymal cell characteristics, including lipid droplet presence and size, between MRL/MpJ and BALB/c mice.
Main Results:
- Significant differences in lateral ventricular volume and surface area were observed among the five mouse strains.
- MRL/MpJ mice displayed the largest volumes across all measured ventricles (lateral, third, aqueduct, and fourth) compared to other strains.
- Neonatal MRL/MpJ mice already possessed larger lateral ventricles than BALB/c mice, indicating early developmental differences.
- While ependymal cell type ratios were similar, MRL/MpJ mice had fewer and smaller lipid droplets in their ependymal cells compared to BALB/c mice.
Conclusions:
- MRL/MpJ mice exhibit inherently larger cerebral ventricles than the other studied strains.
- The observed ventricular enlargement in MRL/MpJ mice, potentially linked to altered ependymal cell function (e.g., reduced endocytosis due to smaller lipid droplets), suggests their utility as a model for hydrocephalus.
- This strain offers a promising avenue for investigating the pathogenesis and potential therapeutic strategies for hydrocephalus.
Abstract:
Hydrocephalus is an intractable disease characterized by the excessive accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles. There are many cases in both human and animals; however, the cause and mechanism of it's development is not clearly understood. In this study, differences of cerebral ventricles in 5 inbred mice strains (MRL/MpJ, C57BL/6, C3H/He, DBA/2 and BALB/c) were investigated by histological techniques to determine the possibility of a new animal model for hydrocephalus. Our analysis showed that significant differences in the volume and the surface area of lateral ventricles in the 5 inbred strains, with MRL/MpJ mice having the largest lateral, third, aqueduct and fourth ventricles. In addition, when MRL/MpJ mice were compared to BALB/c mice on 0 day after birth, the former already had larger lateral ventricles than the latter. Although there were no significant difference in the ratios of ependymal cell types in MRL/MpJ mice and BALB/c mice, the number and the diameter of lipid droplets in MRL/MpJ mice were, interestingly, smaller than those in BALB/c mice. It is well known that ependymal cells absorb nutritional substances in CSF by endocytosis, suggesting the possibility that their decrease may relate to the larger cerebral ventricles in MRL/MpJ. In conclusion, MRL/ MpJ mice have greater volumes in cerebral ventricles than other strains and may be useful for a model showing high susceptibility to hydrocephalus.
