Recent research has aimed to enhance the regeneration capacity of adult cardiomyocytes (CMs), in part by addressing their withdrawal from the cell cycle following myocardial infarction (MI). As a suggested regulator of endogenous CM proliferation, microRNA-128 (miR-128) was investigated as a potential therapeutic target for heart regeneration.
Conditional Knockout of miR-128 Promotes Cardiomyocyte Proliferation
Cardiac-specific, TAM inducible miR-128 knockout mice were generated: administration of TAM was performed at P21 to induce the miR-128 KO at the adult stage – designated as iKO mice1. These iKO mice had unchanged cardiac morphology and normal heart functions, demonstrating that the deletion of miR-128 in the adult heart has no impact on heart function. In addition to dedifferentiation and enhanced proliferation, iKO hearts showed significantly less fibrosis (compared to control) 4 weeks after simulated MI. Furthermore, iKO mice afflicted with MI exhibited a significant reversal of both diminished cardiac function, evidenced by increased EF and FS, and also cardiac remodeling, shown by reduced LVDd and LVDs.
The referenced custom mouse models for both conditional overexpression and conditional deletion of miR-128 were developed by Cyagen to help provide the in vivo platforms for this research and reveal this as a potential avenue for therapeutic advances in cardiac regeneration.
Custom Rodent Models to Further Cardiology Research
The ROSA26 “safe harbor” locus was used in the referenced publication to analyze the dedifferentiation of cells in the myocardial lineage – this locus provides ubiquitous expression of genes inserted without insertion side effects. Cyagen provides guaranteed delivery of custom mouse and rat models for ROSA26 knockin with inserted fragment up to 6kb – tell us the name of the gene(s) you wish to knockin and we will design a nuclease-mediated strategy for you.
Rat models provide a different set of advantages for those investigating cardiac therapies, including more prominent hearts and different gene homologies with humans (than those of mice). If you prefer to work with rat models (due to their larger size and more developed tissue structure), we can help you design and generate the same models using our newly launched RapidKnockout technology. For over-expression of your gene, our PiggyBac-based transgenic technology can generate single-copy transgenic founders with more consistent expression in as fast as 3 months.
References
- Huang, Wei, et al. “Loss of MicroRNA-128 Promotes Cardiomyocyte Proliferation and Heart Regeneration.” Nature Communications, vol. 9, no. 1, 16 Feb. 2018, doi:10.1038/s41467-018-03019-z.
Generation of Custom Genetically Modified Animal Models:
TurboKnockout® Knockout Mice: ES cell mediated, As fast as 6 months, No off-target effects
CRISPR-Pro Knockout Mice: As fast as 3 months, Guaranteed germline transmitted F1 mice
Transgenic Mice: Quick turnaround time, High expression level
PiggyBac Transgenic Mice: More consistent expression, Defined region of integration, As fast as 3 months
CRISPR Knockin Mice: Large fragment up to 8kb, As fast as 4 months
