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Two-Pore Channels: Lessons from Mutant Mouse Models.

Margarida Ruas¹, Antony Galione¹, John Parrington¹

¹Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.

Messenger (Los Angeles, Calif. : Print)

|June 23, 2016

Summary

This summary is machine-generated.

This review assesses two-pore channel (TPC) knockout mouse models, evaluating their utility in understanding TPC functions. It highlights how these models confirm known roles and reveal new physiological functions of TPCs.

Keywords:

Acrosome Arrhythmia Autophagy Cardiac Hypertrophy Endo-Lysosomes Knockout Metabolism Myocardial Infarction Neoangiogenesis Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP)PI(3,5)P2 Reporter Gene Trafficking Two-Pore Channels (TPCN, TPC)

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Area of Science:

Cell Biology
Physiology
Genetics

Background:

Two-pore channels (TPCs) are endo-lysosomal proteins with crucial roles in physiological processes.
Mutant mouse lines for TPCN genes have been generated to study TPC functions in vivo.
Varied genetic strategies and characterization levels necessitate an assessment of these mouse models.

Purpose of the Study:

To review and assess existing TPC knockout mouse lines.
To evaluate the predicted impact of genetic modifications on TPC expression.
To discuss the consolidation of known TPC functions and the discovery of novel roles.

Main Methods:

Literature review of studies utilizing TPC knockout mouse lines.
Analysis of genetic strategies employed in generating mutant mouse lines.
Evaluation of the characterization of TPC expression in these models.

Main Results:

Summarizes TPC knockout mouse lines and their characterization.
Confirms previously proposed roles for TPCs in NAADP signaling, lysosomal function, and pancreatic beta cells.
Identifies new roles for TPCs in membrane excitability, angiogenesis, viral infection, and metabolic/cardiac function.

Conclusions:

TPC knockout mouse lines are valuable tools for studying TPC functions.
These models have validated known TPC roles and uncovered novel physiological functions.
Further characterization of TPC expression in mutant lines is important for accurate interpretation of results.