Reeler

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Reeler lamination

Corticogenesis in a wild-type mouse with captions in english copy

Corticogenesis in reeler mutant mouse with captions in english

Reeler is a term associated with a genetic mutation found in mice, which has significant implications for neuroscience and the study of neurodevelopmental disorders. The reeler mutation affects the migration of neurons during brain development, leading to a disorganized cerebral cortex and cerebellum. This mutation is located in the reelin gene, which encodes for the extracellular matrix protein reelin. Reelin plays a crucial role in regulating the layering of neurons in the developing brain. The study of reeler mice has provided valuable insights into the mechanisms of brain development, the pathogenesis of certain neurological disorders, and the potential for therapeutic interventions.

Genetics and Molecular Biology

The reeler mutation is an autosomal recessive trait, meaning that two copies of the mutant gene are required for the phenotype to be expressed. The gene affected by the reeler mutation is called RELN, which stands for reelin. Reelin is a large secreted protein that signals to migrating neurons and controls cell positioning in the brain by interacting with specific receptors on the surface of neurons, such as the very low-density lipoprotein receptor and the apolipoprotein E receptor 2.

Pathophysiology

In reeler mice, the absence or functional deficiency of reelin leads to a failure in the normal layering process of neurons in the cerebral cortex and cerebellum. Instead of migrating to their correct locations, neurons remain in inappropriate positions, resulting in a reversed cortical layering or a "reeler" phenotype. This disorganization of brain layers disrupts neural connectivity and affects the function of the brain, leading to impairments in motor coordination, learning, and other cognitive functions.

Clinical Significance

The reeler mouse model has been instrumental in understanding the genetic and molecular basis of neuronal migration disorders and has implications for human diseases. Mutations in the RELN gene in humans have been associated with various neurodevelopmental disorders, including autism, schizophrenia, and lissencephaly. Studying the reeler mouse has helped identify potential molecular targets for therapeutic intervention in these conditions.

Research and Therapeutic Implications

Research on reeler mice has not only advanced our understanding of brain development but also opened new avenues for the treatment of neurodevelopmental disorders. By elucidating the pathways through which reelin operates, scientists are exploring potential therapies that could mimic reelin's function or enhance its activity in the brain. Such therapeutic strategies could potentially ameliorate the symptoms or alter the progression of disorders associated with impaired neuronal migration.