Conditional knockout mouse model for studying autosomal-dominant optic atrophy

This technology is a genetically engineered mouse model carrying a patient-specific SSBP1 mutation with a conditional knockout allele that enables the study of cell-type-specific mechanisms of autosomal-dominant optic atrophy and retinal degeneration.

Unmet Need: Mouse model for physiologically relevant autosomal-dominant optic atrophy research

Autosomal-dominant optic atrophy-13 (OPA13) is characterized by decreased visual perception and retinal degeneration, yet the specific triggering factors remain unclear. Current research often relies on zebrafish models; however, these models have produced conflicting findings regarding whether pathogenic variants result in haploinsufficiency or dominant-negative effects. There is a critical need for a physiologically relevant mammalian system to resolve these mechanistic discrepancies and enable the investigation of retinal ganglion cell and photoreceptor abnormalities.

The Technology: Genetically engineered mouse model enabling cell-type-specific disease mechanism studies

This technology is a genetically engineered mouse model that contains a Ssbp1 knock-in allele that converts arginine (R) 107 to glutamine (Q), replicating a common variant found in human OPA13 patients. The mutation is flanked by loxP sites (floxed), allowing researchers to delete or activate the mutant allele in specific cell types when crossed with Cre recombinase driver lines. This conditional design enables investigation of whether the R107Q variant causes disease through haploinsufficiency or dominant-negative mechanisms, and allows researchers to determine which retinal cell populations are critical for disease progression.

This technology has been validated through optical coherence tomography and electroretinography studies in mice.

Applications:

  • Therapeutic screening platform for retinal disease interventions
  • Model for identifying novel therapeutic targets
  • Research tool for studying autosomal-dominant optic atrophy disease mechanisms
  • Research tool for analyzing the role of SSBP1 mutations in cancer biology
  • Cell-type-specific analysis of retinal ganglion cell and photoreceptor degeneration pathways

Advantages:

  • Models a clinically relevant phenotype for retinal degeneration
  • Models progressive retinal degeneration
  • Versatile genetic tool to study mutant protein deletion
  • Compatible with widely used Cre driver lines
  • Mammalian model organism is more physiologically relevant than zebrafish

Lead Inventor:

Nan-Kai Wang, M.D., Ph.D.

Tech Ventures Reference: