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Updated: Aug 29, 2026
Genetic Manipulation of the Mouse Developing Hypothalamus through In utero Electroporation
Published on: July 24, 2013
MRI and in situ hybridization reveal early disturbances in brain size and gene expression in the megencephalic
Margarita Diez1, Petra Schweinhardt, Susanna Petersson
1Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden. Margarita.Diez@neuro.ki.se
Abstract:
The mouse model for megencephaly, mceph/mceph, carries a truncating deletion in the Shaker-related voltage gated potassium channel gene 1. Affected mice display neurological disturbances and motor dysfunctions. Symptoms begin to show at 3-4 weeks of age. The cause of the brain enlargement is not clear. To elucidate early events in the development of the disease we used magnetic resonance imaging (MRI) to quantify, over time, the increase in size of several discrete brain regions in the same mice at 3, 8 and 12 weeks of age. We also analysed markers for neuropeptides and growth factors to explore their possible involvement at an early stage. The results show an enlargement of the total coronal area of the brain already at 3 weeks of age. Total brain volume, ventral cortex, hippocampal formation and cerebral cortex were enlarged at 8 weeks and onwards. Thalamus, brainstem, cerebellum and spinal cord did not differ from controls even at 12 weeks. We also report distinct disturbances in the expression of brain-derived neurotrophic factor, insulin-like growth factor binding protein 6 and several neuropeptides at 2 and 3 weeks of age, that is, before an obvious behavioural phenotype can be observed. These results provide an objective description of the size changes in different brain regions of the mceph/mceph mouse, and suggest that certain molecules could be involved in the early processes underlying these changes.
Insights
The mceph/mceph mouse model shows early brain enlargement and molecular changes before observable symptoms, offering insights into megencephaly development. This research highlights key brain regions affected by this genetic condition.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- The mceph/mceph mouse model exhibits megencephaly due to a deletion in the Shaker-related voltage-gated potassium channel gene 1.
- Affected mice display neurological disturbances and motor dysfunctions starting around 3-4 weeks of age.
- The underlying cause of brain enlargement in this model remains unclear.
Purpose of the Study:
- To investigate the early developmental events leading to brain enlargement in the mceph/mceph mouse model.
- To quantify volumetric changes in specific brain regions over time using magnetic resonance imaging (MRI).
- To explore the potential involvement of neuropeptides and growth factors in the early stages of the disease.
Main Methods:
- Longitudinal MRI scans were performed on mceph/mceph mice at 3, 8, and 12 weeks of age to measure brain region volumes.
- Analysis of neuropeptide and growth factor markers was conducted at 2 and 3 weeks of age.
- Comparison of brain region sizes and molecular markers between affected mice and control groups.
Main Results:
- Brain enlargement, indicated by an increased total coronal area, was detected as early as 3 weeks of age.
- Significant enlargement of total brain volume, ventral cortex, hippocampal formation, and cerebral cortex was observed from 8 weeks onwards.
- No significant size differences were found in the thalamus, brainstem, cerebellum, or spinal cord compared to controls, even at 12 weeks.
- Disturbances in the expression of brain-derived neurotrophic factor, insulin-like growth factor binding protein 6, and several neuropeptides were identified at 2-3 weeks of age, preceding behavioral phenotype.
Conclusions:
- The mceph/mceph mouse model displays region-specific brain enlargement starting early in development.
- Molecular changes involving specific growth factors and neuropeptides occur before overt neurological symptoms.
- These findings suggest that early molecular events play a crucial role in the pathogenesis of megencephaly in this model.
