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Hyperactive and impulsive behaviors of LMTK1 knockout mice
Miyuki Takahashi1,2, Arika Sugiyama1, Ran Wei1
1Laboratory of Molecular Neuroscience, Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Minami-osawa, Hachioji, Tokyo, 192-0397, Japan.
Scientific Reports
|September 23, 2020
Summary
Lemur tail kinase 1 (LMTK1) knockout mice show increased synapses and altered behaviors, including hyperactivity and impulsivity. These findings suggest LMTK1
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Lemur tail kinase 1 (LMTK1), also known as Apoptosis-Associated Tyrosine Kinase (AATYK), is a brain-predominant Ser/Thr protein kinase.
- LMTK1A, an isoform, interacts with recycling endosomes and regulates endosomal trafficking by inhibiting Rab11 GTPase.
- Previous studies indicated LMTK1 influences neuronal morphology, with knockdown/knockout leading to longer axons and increased dendritic branching.
Purpose of the Study:
- To investigate the in vivo function of LMTK1 in the brain.
- To characterize the brain structure and behavioral phenotypes of LMTK1 knockout (KO) mice.
Main Methods:
- Generation and analysis of LMTK1 knockout (KO) mice.
- Assessment of brain structure, including synapse numbers.
- Behavioral testing to evaluate memory, motor coordination, and psychiatric-like behaviors.
Main Results:
- LMTK1 is broadly expressed in neurons across the brain.
- LMTK1 KO mice exhibit normal overall brain structure but increased synapse numbers.
- LMTK1 KO mice display impaired memory, hyperactivity, impulsivity, and high motor coordination, without social deficits.
Conclusions:
- LMTK1 plays a significant role in regulating synaptic structure and neuronal function in vivo.
- The behavioral phenotype of LMTK1 KO mice, including hyperactivity and impulsivity, suggests a potential involvement in attention deficit hyperactivity disorder (ADHD) pathogenesis.
- Further research into LMTK1's role could elucidate mechanisms underlying neurodevelopmental disorders.
