Generation of Common Marmoset Model Lines of Spinocerebellar Ataxia Type 3

Abstract

Animal models are indispensable tools in the development of innovative treatments for rare and incurable diseases. To date, there is almost no effective treatment for neurodegenerative diseases, and animal models that properly simulate human disease pathologies are eagerly anticipated to identify disease biomarkers and develop therapeutic methods and agents. Among experimental animals, non-human primates are the most suitable animal models for the study of neurodegenerative diseases with human-specific higher brain dysfunction and late-onset and slowly progressing symptoms. With the rapid development of novel therapies such as oligonucleotide therapeutics and genome editing technologies, non-human primate models for neurodegenerative diseases will be essential for preclinical studies and active interventional trials. In a previous publication, we reported the generation of the first transgenic marmoset model of spinocerebellar ataxia type 3 and successful obtainment of subsequent generations with stable disease onset. Moreover, we generated transgenic marmosets in which the transgene was controlled by the tetracycline-inducible gene expression system. In this mini-review, we summarize the research on our marmoset model of spinocerebellar ataxia type 3.

Flexible auditory training, psychophysics, and enrichment of common marmosets with an automated, touchscreen-based system

“…Notably, the common marmoset ( Callithrix jacchus ) has become a valuable model for biomedical research in general and the neurosciences in particular 19 – 21 . Factors such as the relative ease of breeding, early sexual maturation and short life span 22 , 23 have contributed to the rapid generation of genetic models of human mental and neurological diseases in marmosets 1 , 24 – 26 . While generally marmoset training is lacking behind the sophistication of cognitive NHP experiments traditionally performed with macaques, auditory capabilities of marmosets have been investigated extensively 27 – 32 .…”

Advances in Modeling Polyglutamine Diseases Using Genome Editing Tools

“…Additionally, the models explore genetic pathways and mechanisms underlying disease development such as expansions, aberrant splicing, repeat-associated non-AUG (RAN) translation and RNA frameshifting. By using methods such as lentiviral transduction, microinjection with mRNA and transposase-mediated recombination, transgenic models were generated in yeast [87,88], human embryonic kidney (HEK) 293T cells [89][90][91], C. elegans [92][93][94][95], D. melanogaster [96][97][98], zebrafish [99][100][101][102], the mouse [27,[103][104][105][106][107][108][109][110][111][112][113], rat [83,114], sheep [115], pig [116,117] and monkey [118][119][120][121]. Additionally, patient-derived cells were reprogrammed into iPSCs and used to model polyQ diseases [122][123][124][125][126][127][128].…”

Understanding and Treating Niemann–Pick Type C Disease: Models Matter

“…There are numerous reasons for the slow progress such as rare occurrence, molecular complexity, and variability of symptoms. However, a decisive factor is the availability, quality, and use of experimental models [4][5][6][7][8][9][10][11][12][13]. NPC is a prime example for a disease that lacks a curative therapy despite impressive breakthroughs within the last decades [14][15][16][17] and rapidly growing publication counts (Appendix A, Figure 1).…”