Slitrk1-KO Mouse

Slitrk1, or SLIT and NTRK-like 1, is a gene encoding a neuronal transmembrane protein. It has functions in controlling neurite development, synaptic formation, and is involved in noradrenergic and serotonergic systems [2]. It is associated with several neuropsychiatric disorders such as obsessive-compulsive disorder spectrum-disorders, Tourette's syndrome, trichotillomania, bipolar disorder, and schizophrenia [1,2,3]. Genetic models, especially mouse models, are valuable for studying its role.

In Slitrk1-KO mouse models, several significant findings have emerged. Newborns show abnormal vocalizations, with their prefrontal cortices having excessive noradrenergic neurites, reduced Semaphorin3A expression, increased noradrenaline levels, and enlarged serotonergic varicosities [1]. These mice also exhibit anxiety-like behaviors later in life, which can be attenuated by an alpha 2 noradrenergic receptor agonist [2]. In adult mice, conditional knockdown of Slitrk1 in striatal cholinergic neurons leads to TS-like tic behaviors, impaired prepulse inhibition, and changes in dopaminergic and cholinergic transmission [4]. Deletion of Slitrk1 in mice also results in elevated anxiety-like behavior and increased levels of norepinephrine and its metabolite [5].

In conclusion, Slitrk1 is crucial for normal development of neural circuits related to noradrenergic and serotonergic systems. Studies using Slitrk1 KO/CKO mouse models have revealed its significance in neuropsychiatric disorders like Tourette's syndrome, obsessive-compulsive disorder, and related conditions, highlighting its potential as a therapeutic target for these diseases.

References:

1. Hatayama, Minoru, Katayama, Kei-Ichi, Kawahara, Yukie, Yoshikawa, Takeo, Aruga, Jun. 2022. SLITRK1-mediated noradrenergic projection suppression in the neonatal prefrontal cortex. In Communications biology, 5, 935. doi:10.1038/s42003-022-03891-y. https://pubmed.ncbi.nlm.nih.gov/36085162/

2. Hatayama, Minoru, Aruga, Jun. 2023. Developmental control of noradrenergic system by SLITRK1 and its implications in the pathophysiology of neuropsychiatric disorders. In Frontiers in molecular neuroscience, 15, 1080739. doi:10.3389/fnmol.2022.1080739. https://pubmed.ncbi.nlm.nih.gov/36683853/

3. Lin, Wei-De, Tsai, Fuu-Jen, Chou, I-Ching. 2022. Current understanding of the genetics of tourette syndrome. In Biomedical journal, 45, 271-279. doi:10.1016/j.bj.2022.01.008. https://pubmed.ncbi.nlm.nih.gov/35042017/

4. Du, Jung-Chieh, Chang, Man-Hsin, Yeh, Chen-Jiun, Chuang, Shu-Hui, Chiou, Lih-Chu. 2023. Pivotal Role of Slitrk1 in Adult Striatal Cholinergic Neurons in Mice: Implication in Tourette Syndrome. In Annals of neurology, , . doi:10.1002/ana.26805. https://pubmed.ncbi.nlm.nih.gov/37776102/

5. Katayama, K, Yamada, K, Ornthanalai, V G, Murphy, N P, Aruga, J. 2008. Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities. In Molecular psychiatry, 15, 177-84. doi:10.1038/mp.2008.97. https://pubmed.ncbi.nlm.nih.gov/18794888/