Trank1-KO Mouse

TRANK1, also known as Tetratricopeptide repeat and ankyrin repeat containing 1, has been associated with multiple psychiatric disorders. Although its neuronal function remains relatively unclear, genes highly correlated with TRANK1 are significantly enriched in biological processes related to dendritic spine, synaptic plasticity, axon guidance and circadian entrainment [2].

Genetic analyses have confirmed TRANK1 as a susceptibility gene for bipolar disorder (BD). Lower TRANK1 mRNA expression is a principal BD risk factor [2]. In BD, administration of type 1 interferon can induce the expression of TRANK1, which is associated with elevated circulating biomarkers of the impaired blood-brain barrier. Intestine microbiota-dependent type 1 interferon signalling may induce over-expression of TRANK1, compromising blood-brain barrier integrity and contributing to BD pathogenesis [1]. Also, in a mice model, fecal microbiota transplantation from BD patients led to a depression-like phenotype with elevated TRANK1 mRNA levels in the hippocampus and prefrontal cortex [3].

In Kleine-Levin syndrome (KLS), a genome-wide association study found a strong association within the 3' region of the TRANK1 gene locus, and the gene polymorphisms in conjunction with birth difficulties may predispose to KLS [5]. In schizophrenia, increased plasma IgG antibodies against TRANK1-derived peptide antigens were observed, suggesting it could be a biomarker for a subgroup of schizophrenia [4].

In conclusion, TRANK1 is significantly associated with psychiatric disorders such as bipolar disorder, Kleine-Levin syndrome, and schizophrenia. Through genetic analyses and animal models, it has been revealed that TRANK1 may play important roles in these disorders, potentially by affecting blood-brain barrier integrity, being associated with circadian regulation, and serving as a biomarker. The study of TRANK1 helps to better understand the pathophysiology of these psychiatric diseases and may provide new targets for treatment.