Mouse models as a tool for discovering new neurological diseases

Area of Science:

• Genetics
• Genomic Medicine
• Translational Research

Background:

• Animal models are crucial for biological and medical research.
• Mice, a common model organism, are underutilized for predicting human diseases.
• Gene dosage alterations in model organisms can reveal insights into human genetic disorders.

Purpose of the Study:

• To highlight the value of mouse models in discovering human genetic syndromes.
• To present examples of gene dosage studies in mice leading to human disease identification.
• To discuss resources facilitating the translation of model system findings to human disease gene discovery.

Main Methods:

• Reviewing research on gene dosage alterations in mouse models.
• Analyzing four specific examples: MECP2 duplication, SHANK3 duplication, CIC haploinsufficiency, and PUM1-related disorders.
• Describing clinical phenotypes of previously unreported individuals with CIC haploinsufficiency syndrome.

Main Results:

• Studies of gene dosage in mice identified novel human syndromes, including MECP2 duplication, SHANK3 duplication, CIC haploinsufficiency, and PUM1-related disorders.
• Two new cases of CIC haploinsufficiency syndrome were clinically characterized.
• The bidirectional approach between mouse models and human studies accelerates disease gene discovery.

Conclusions:

• Mouse models are powerful tools for identifying and understanding human genetic diseases.
• Translational research, moving between model systems and clinical studies, is key to advancing genetic disease discovery.
• This approach provides a foundation for developing future therapeutic interventions for genetic disorders.