Rats cannot naturally develop Down syndrome, as this genetic condition is unique to humans. However, scientists have developed specialized rat models that mimic aspects of the condition to advance understanding and potential treatments.
The Genetic Basis of Down Syndrome
Down syndrome in humans results from Trisomy 21, meaning an extra copy of chromosome 21. Humans have 23 pairs of chromosomes, while rats typically have 21 pairs.
The genes on human chromosome 21 are not found on a single corresponding chromosome in rats. Instead, these genes are scattered across several rat chromosomes, such as 10, 11, and 18. Due to this fundamental difference, Trisomy 21 cannot naturally occur in rats.
Creating a Rat Model for Research
Despite natural genetic differences, scientists have developed genetically engineered animal models to study Down syndrome. The aim is to replicate the “gene dosage” effect, where an excess of certain genes leads to characteristics similar to the human condition. A primary rat model introduced for this purpose is the TcHSA21rat.
This model contains a human chromosome 21 (HSA21) within the rat’s cells. Scientists use advanced genetic techniques to insert this entire human chromosome, which carries over 93% of its protein-coding genes, into the rat genome. This creates a rat with an additional copy of human chromosome 21.
The Purpose of Rat Models in Down Syndrome Research
The TcHSA21rat model exhibits characteristics analogous to features observed in humans with Down syndrome. These engineered rats show difficulties with learning and memory, alongside increased anxiety and hyperactivity. They also display brain morphology changes, including smaller brain volume and reduced cerebellar size, and notably, reduced cerebellar foliation, a feature not typically observed in mouse models.
Rat models offer distinct advantages over other animal models, such as mice, in certain research areas. Rats possess more complex cognitive functions and social behaviors, making them better suited for investigating higher-order thinking processes. Their larger body and organ size also facilitate more precise imaging, surgical procedures, and physiological interventions. Additionally, rat organ morphology, including cerebellar structures, shows greater similarity to humans than that of mice, providing more robust physiological and behavioral data.
These models are valuable for studying how the extra genes on human chromosome 21 influence brain development and function. Researchers use them to test the safety and effectiveness of new medications or non-pharmacological therapies. The ultimate goal is to improve cognitive outcomes and enhance the quality of life for individuals with Down syndrome, accelerating drug development through preclinical validation.