At Ace Therapeutics, we specialize in constructing custom animal models to support glaucoma research. Our expertise in genetic engineering enables the development of transgenic TBK1 mouse models that replicate the complex pathophysiology of glaucoma, serving as powerful tools for investigating disease mechanisms and testing novel drugs.
TBK1 Function in Normal Tension Glaucoma
TANK-binding kinase 1 (TBK1) is a multifunctional kinase implicated in various cellular processes, including innate immunity, autophagy, and cell survival. Recent studies have linked TBK1 copy number variations (CNVs) to normal tension glaucoma (NTG), a condition characterized by progressive retinal ganglion cell (RGC) death despite normal intraocular pressure (IOP). TBK1 gene duplication and triplication have been identified in NTG patients across diverse populations, suggesting a gain-of-function mechanism in glaucoma pathogenesis. Transgenic mice overexpressing TBK1 exhibit key features of NTG, including progressive RGC loss without elevated IOP, making TBK1 an attractive target for glaucoma research.
Fig. 1 Increased TBK1 protein in the Tg-TBK1 mouse retina. (Fingert J H, et al., 2017)
Explore Our Transgenic TBK1 Mouse Models of Glaucoma
Our experienced experts generate transgenic mice by introducing the full-length human TBK1 gene, including its promoter, exons, and introns into the mouse genome. This results in mice with an extra copy of the TBK1 gene, modeling the TBK1 gene duplication observed in human NTG. Exhibiting progressive RGC loss, our transgenic TBK1 mouse models can be used to investigate the impact of elevated TBK1 activity on glaucoma pathogenesis.
Comprehensive Transgenic TBK1 Mouse Model Validation Services
Ace Therapeutics offers comprehensive model validation services to ensure the utility of our transgenic TBK1 mouse models in glaucoma research and therapeutic development.
- IOP measurement
We offer IOP measurement services to determine whether the RGC loss in our transgenic TBK1 mice occurs independently of elevated IOP, mirroring the pathology observed in NTG. - RGC analysis
Our team employ rigorous methods to assess RGC health in our transgenic TBK1 mouse models. We quantify RGC loss through cell counting to characterize the progression of glaucoma in our mouse models as well as use immunohistochemistry to localize and analyze TBK1 protein expression within the ganglion cell layer, the primary site of damage in glaucoma. - TBK1 transgene expression analysis
We provide real-time PCR services to quantify the expression of the human TBK1 transgene in the retina of our transgenic TBK1 mouse models.
Ace Therapeutics is committed to supporting preclinical drug development for glaucoma through the development of genetic mouse models. Our transgenic TBK1 mouse models exhibit progressive RGC loss, recapitulating the phenotype of human NTG. Contact us today to explore the molecular mechanisms of glaucoma and evaluate potential therapeutics with our support.
Reference
- Fingert J H, et al. Transgenic TBK1 mice have features of normal tension glaucoma. Hum Mol Genet, 2017, 26(1): 124-132.