Mouse model for ion channel disruption via TRIP8b disruption

This technology describes an inducible mouse line for the expression of unstable TRIP8b protein to study ion channel localization and function.

Unmet Need: Selective disruption of ion channels in heart and brain cells

Ion channel expression and localization is key to a neuron’s electrical activity in distinct regions of the cell. However, changes in the localization or level of channel present in a brain or spinal cord cell can result in neurological diseases. One type of channel, which has differential localization patterns in some disease states, is the hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel. There is need for an animal model to evaluate the regulation and localization of HCN ion channels in heart and brain cells.

The Technology: Mouse model for studying HCN ion channels using TRIP8b

This technology describes a mouse line with inducible expression of an unstable TRIP8b protein in a cell type specific manner. This mouse model is engineered to delete the coding exon of the TRIP8b subunit, a brain specific subunit required for hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel function. As such, this technology provides an in vivo model to assess mechanisms of HCN localization and its role in numerous disease states.

Applications:

• In vivo model for studying TRIP8b protein
• Research tool for assessing hyperpolarization-activated cyclic nucleotide-gated (HCN) channel expression in the brain and spinal cord
• Screening drugs and evaluating the efficacy of treatments
• Mouse line for genetic crossings with other mouse models

Advantages:

• Tissue-specific inducible transgene expression
• Ability to perform in vivo and ex vivo experiments
• Physiologically relevant model to study ion channel expression in heart and brain cells
• Homozygous animals are viable and fertile
• Compatible with crossing to other conditional transgenic mutants

Lead Inventor:

Steven A. Siegelbaum, Ph.D.

Related Publications:

• Srinivas KV, Buss EW, Sun Q, Santoro B, Takahashi H, Nicholson DA, Siegelbaum SA. “The dendrites of CA2 and CA1 pyramidal neurons differentially regulate information flow in the cortico-hippocampal circuit.” Journal of Neuroscience. 2017 Mar 22; 37(12): 3276-93.

Tech Ventures Reference:

• IR CU23232
• Licensing Contact: Jerry Kokoshka