Lessons from tau-deficient mice.

Area of Science:

• Neuroscience
• Genetics
• Pathology

Background:

• Alzheimer's disease (AD) and frontotemporal dementia (FTD) are tauopathies characterized by hyperphosphorylated tau pathology.
• Transgenic mouse models expressing human tau have advanced understanding of tau's role in disease.
• Tau knockout mouse strains have been developed to investigate the physiological functions of tau.

Purpose of the Study:

• To review literature on tau knockout mice to summarize findings from in vivo tau depletion.
• To understand the physiological functions of tau.
• To elucidate the role of tau in neurodegenerative conditions.

Main Methods:

• Generation and analysis of multiple tau knockout mouse strains with MAPT gene deletion.
• In vivo and in vitro studies using tau-depleted models.
• Behavioral and motor deficit assessments in aged tau knockout mice.

Main Results:

• Initial tau knockout mice showed no overt phenotype.
• Recent studies identified behavioral changes and motor deficits in aged tau knockout mice.
• Tau knockout models have revealed novel tau functions and elucidated the Aβ-tau interplay in AD.

Conclusions:

• Tau knockout mice are crucial tools for understanding tau physiology and pathophysiology.
• Depleting tau in vivo has provided significant insights into neurodegenerative disease mechanisms.
• Further research with tau knockout models is essential for advancing AD and FTD therapeutics.