Based on a GWAS assessment, the human gene RIMS1 has been tentatively identified as a susceptibility locus for the development of schizophrenia. RIMS1 is one of several related human genes that regulate synaptic membrane exocytosis. This model uses the single orthologous gene in Drosophila, Rim, for which for which a variety of genetic reagents have been generated, including loss-of-function mutations, RNAi targeting constructs, and alleles caused by insertional mutagenesis.
Dmel\Rim is also orthologous to the other human genes in this family, RIMS2, RIMS3, and RIMS4. A UAS construct of the human Hsap\RIMS2 gene has been introduced into flies but has not been characterized. None of the other human genes has been introduced into flies.
Animals homozygous for loss-of-function alleles of Dmel\Rim are generally viable, but may exhibit developmental delay. Since olfactory impairments are widely reported in patients with schizophrenia, the olfactory acuity of loss-of-function genotypes of Dmel\Rim was assessed; a reduction in olfactory acuity was observed. Animals with a loss-of-function genotype of Rim also exhibit circadian locomotor activity deficits and increased social distance in an assay to assess social space behavior.
RIMS1 is one of a number of genes in human that have been implicated in both autism spectrum disorder and schizophrenia. See the human disease model reports 'autism spectrum disorder, susceptibility to, RIMS-related' (FBhh0001277) and 'autism co-occurence with schizophrenia' (FBhh0001356).
[updated Jun. 2021 by FlyBase; FBrf0222196]
See also 'Schizophrenia: Symptoms, causes, and treatments' (http://www.medicalnewstoday.com/articles/36942.php).
Schizophrenia is a psychosis, a disorder of thought and sense of self. Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Schizophrenia often develops in young adults who were previously normal, and is characterized by a constellation of symptoms including hallucinations and delusions (psychotic symptoms) and symptoms such as severely inappropriate emotional responses, disordered thinking and concentration, erratic behavior, as well as social and occupational deterioration (Andreasen, 1995; pubmed:7637483). [from MIM:181500; 2017.04.18]
Although loss of olfaction is often observed in schizophrenia (Rupp, 2010; pubmed:20051859), the opposite, heightened olfactory sensitivity, is frequently observed in autism (Ashwin et al., 2014; pubmed:25908951).
The protein encoded by RIMS1 is a RAS gene superfamily member that regulates synaptic vesicle exocytosis; it may be required for maintaining normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity. [Gene Cards, RIMS1; 2020.11.03]
Many to one: 4 human genes to 1 Drosophila gene; the human genes are RIMS1, RIMS2, RIMS3, and RIMS4.
