Transgenic Models of Neurodegenerative Disease

The increasing incidence of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) have become one of the most challenging health problems for aging humans. Using genetically modified animal models of neurodegenerative diseases to study pathogenesis, prognosis, diagnosis, treatment, and prevention is one of the main methods in current biomedical.

Neurodegenerative Transgenic Animal Models in Mice

Neurodegenerative diseases, including motor neuron disease (MND), AD, PD, prion disease, Huntington's disease (HD) and cerebellar ataxia. It is autosomal dominant and age-related, including specific gene mutations disease. Due to the development of in vitro systems and advances in transgenic technology, researchers have created transgenic animal models of these diseases. At present, genetically modified models of neurodegenerative diseases are the most common in mice.

Table 1. Transgenic mouse models for neurodegenerative diseases.

The transgenic mouse model is the most used mammalian genetic model because of its high efficiency, economy, and ease of operation. Although the phenotype and neuronal pathology of various transgenic mouse models in neurodegenerative diseases have been extensively studied, none of them exhibits as strong neurodegeneration as the human brain.

Fig.1 A mouse model that expresses mHtt in different types of neurons or glial cells. (Chang, 2015)

Neurodegenerative Transgenic Animal Models in Other Primates

Large-scale transgenic animal models have been established in non-human primates, such as rhesus monkeys, pigs, sheep, and chickens. Due to the genetic, anatomical, physiology, pathological and neurological similarities between large mammals and humans, large-scale transgenic animal models are highly attractive in neurodegenerative diseases and can bridge the gap between rodents and humans in preclinical research.

No matter how perfect an animal model is, it cannot completely replicate the phenotype of human neurodegenerative diseases. Significant progress has been made in using transgenic methods to simulate human neurodegenerative diseases in animals and transform them into human targeted therapy. These transgenic models provide basic biological knowledge and disease phenotypes related to human conditions and provide important information in elucidating the pathogenic mechanism of diseases and developing treatment strategies.

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References

1. Dawson, T.M.; et al. Animal models of neurodegenerative diseases. Nature neuroscience. 2018, 21(10): 1370-1379.
2. Chang, R.; et al. Transgenic animal models for study of the pathogenesis of Huntington’s disease and therapy. Drug design, development and therapy. 2015, 9: 2179.