Columbia Technology Ventures

RbAp48 transgenic mice for drug discover in age-related memory decline

The hippocampus is a brain structure that plays an essential role in the formation and consolidation of episodic memory. It comprises various molecularly distinct regions that are affected differently by ailments such as Alzheimer's disease and normal aging. Given that the molecular defects associated with hippocampal dysfunction are largely unknown, there is a need for genetic tools that can identify the mechanisms underlying this dysfunction. This technology is a mouse model that expresses a defect in histone acetylation, which can be used to study the effect of this pathway on hippocampal dysfunction.

Mouse model provides spatial and temporal control of RbAp48 expression

The technology is a transgenic mouse that expresses a dominant-negative form of RbAp48, a protein that plays a role in the histone acetylation pathway. This enables the expression of RbAp48 in the hippocampus to be spatially and temporally controlled; by inhibiting the expression of the protein in various regions of the hippocampus, the mouse can be used to determine whether defects in histone acetylation lead to hippocampal dysfunction typically associated with age.

This transgenic mouse has been used to show age-dependent memory deficits in the dentate gyrus region of the hippocampus with RbAp48 inhibition, which was ameliorated by up-regulation of RbAp48.

Lead Inventor:

Scott A. Small, M.D.

Applications:

  • A mouse model for studying the molecular mechanisms underlying age-, injury, or disease-related hippocampal dysfunction
  • A mouse model for in vivo testing of therapeutics to treat or prevent hippocampal dysfunction

Advantages:

  • Association of RbAp48 deficiency with hippocampal cognitive dysfunction enables the testing of drugs that can mitigate certain age-related memory deficits
  • Temporal and spatial control of RbAp48 expression

Patent Information:

Patent Pending (US20140294798 A1)

Tech Ventures Reference: IR CU12034

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