De novo frameshift variants in this gene have been identified in unrelated ASD cases from the Simons Simplex Collection (Iossifov et al., 2012; Dong et al., 2014).
Molecular Function
Rab effector involved in exocytosis. May act as scaffold protein that regulates neurotransmitter release at the active zone. Essential for maintaining normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity. Mutations in this gene have suggested to play a role in cognition and have been identified as the cause of cone-rod dystrophy type 7 (CORD7) [MIM:603649].
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.
RIMS1 homozygous knockout mice exhibit a 50% reduction in probability of neurotransmitter release (Schoch S, et al, Nature, 2002). RIMS1 homozygous knockout mice show no change in coordination and anxiety-related behaviors but display severely impaired spatial learning and memory and fear conditioning, partially due to decrease in neurotransmitter release probability and a loss of presynaptic LTP together with presynaptic neuroanatomical abnormalities (Powell CM, et al., Neuron, 2004). RIMS1 mutant mice exhibit decreased prepulse inhibition, exaggerated increase in activity in response to psychotomimetic drugs, and deficits in social interaction with juvenile mice (Blundell J, et al., J. Neurosci, 2010).
References
Type
Title
Author, Year
Primary
RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Mice lacking expression of RIM1-alpha, the full-length transcript of the RIM1 gene and most abundant RIM isoform. The first exon of RIM1-alpha was replaced with a neomycin resistance gene (pTK-Neo3A). Deletion of the first exon abolishes expression because it includes the initiator methionine and 55 conserved N-terminal residues of RIM1-alpha.
Allele Type: Knockout
Strain of Origin: Not reported
Genetic Background: SV129*C57/Bl6
ES Cell Line: Mutant ES Cell Line: E14.1/29S6/SvEvTac
Model Source: Schoch et al, 2002 (PMID 11797009)
Model Type:
Genetic
Model Genotype:
Not reported
Mutation:
Mice where the 413th residue serine of RIMS1 is mutated to alanine.
Allele Type: LOF Knockin
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line: Mutant ES Cell Line: Not reported
Model Source: Kaeser et al, 2008 (PMID 19074017)
Model Type:
Multifactorial
Model Genotype:
Homozygous
Mutation:
Mice lacking the RIMS1 gene were given an intraperitoneal injection of the NMDA receptor antagonist MK-801 (0.1mg/kg) and tested for the effect of the psychomimetic drug on locomotor activity.
Allele Type: Knockout
Strain of Origin: Not reported
Genetic Background: SV129*C57/Bl6
ES Cell Line: Mutant ES Cell Line: E14.1/29S6/SvEvTac
Model Source: Schoch et al, 2002 (PMID 11797009)
Model Type:
Multifactorial
Model Genotype:
Homozygous
Mutation:
Mice lacking the RIMS1 gene were given an intraperitoneal injection of the NMDA receptor antagonist MK-801 (0.1 then 0.2 mg/ kg) and tested for the effect of the psychomimetic drug on locomotor activity.
Allele Type: Knockout
Strain of Origin: Not reported
Genetic Background: SV129*C57/Bl6
ES Cell Line: Mutant ES Cell Line: E14.1/29S6/SvEvTac
Model Source: Schoch et al, 2002 (PMID 11797009)
Model Type:
Multifactorial
Model Genotype:
Not reported
Mutation:
Mice with the 413th residue serine of RIMS1 mutated to alanine, were given an intraperitoneal injection of the NMDA receptor antagonist MK-801 (0.1mg/kg) and tested for the effect of the psychomimetic drug on locomotor activity.
Allele Type: LOF Knockin
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line: Mutant ES Cell Line: Not reported
Model Source: Kaeser et al, 2008 (PMID 19074017)
Model Type:
Multifactorial
Model Genotype:
Not reported
Mutation:
Mice with the 413th residue serine of RIMS1 mutated to alanine, were given an intraperitoneal injection of the NMDA receptor antagonist MK-801 (0.1 then 0.2 mg/ kg) and tested for the effect of the psychomimetic drug on locomotor activity.
Allele Type: LOF Knockin
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line: Mutant ES Cell Line: Not reported
Model Source: Kaeser et al, 2008 (PMID 19074017)
Model Type:
Genetic
Model Genotype:
Not reported
Mutation:
Hippocampus specific knockdown of RIMS1 was achieved by injecting AAV-hSyn-Cre-GFP into the hippocampus of conditional-ready exon 6 RIMS1 floxed mice.
Allele Type: Knockdown
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line: Mutant ES Cell Line: Not reported
Model Source: Kaeser et al, 2008 (PMID 19074017)
Model Type:
Genetic
Model Genotype:
Not reported
Mutation:
3-week old mice injected with lentivirus harboring short-hairpin RNAs in the CA1 hippocampusdemonstrated to knock down endogenous RIMS1 at the post-synaptic membrane specifically.
Allele Type: Knockdown
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line: Mutant ES Cell Line: Not reported
Model Source: Kiyonaka et al, 2007 (PMID 17496890)
Model Type:
Genetic
Model Genotype:
Not reported
Mutation:
3-week old mice injected with lentivirus harboring short-hairpin RNAsdemonstrated to knock down endogenous RIMS1 in the CA3 hippocampus.
Allele Type: Knockdown
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line: Mutant ES Cell Line: Not reported
Model Source: Kiyonaka et al, 2007 (PMID 17496890)
Model Type:
Genetic
Model Genotype:
Not reported
Mutation:
8-week old mice injected with lentivirus harboring short-hairpin RNAs in the CA1 hippocampus demonstrated to knock down endogenous RIMS1 at the post-synaptic membrane specifically.
Allele Type: Knockdown
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line: Mutant ES Cell Line: Not reported
Model Source: Kiyonaka et al, 2007 (PMID 17496890)
Description: Mutants exhibit increased ppd upon presynaptic paired-pulse stimulation at short inter stimulus intervals, compared to controls, indicating deleting rims1 decreases transmitter release during paired stimulations at inhibitory synapses.
Exp Paradigm: Monosynaptic inhibitory postsynaptic currents were recorded from ca1 pyramidal neurons in response to paired-pulse stimuli in the stratum radiatum.
Description: Mutants show continually decreased nmdar-mediated excitatory postsynaptic currents (epscs) upon repetitive stimulation of excitatory synapses in the presence of mk-801, compared to controls, with the rate of decrease being directly proportional to the probability of neurotransmitter release. mutants show a probability of release (pr) half that in controls, measured by the difference in the decay constants.
Exp Paradigm: Probability of neurotransmitter release was measured by the mk-801 method. inhibitor mk-801 irreversibly blocks nmdars, but only when they are activated by synaptically released glutamate.
Description: Mutants exhibit extended facilitation upon repetitive stimulation of excitatory synapses whereas control synaptic responses exhibit initial facilitation that slowly decreases. mutants exhibit increased post-tetanic potentiation, compared to controls.
Exp Paradigm: Repetitive stimulations of excitatory synapses at moderate frequencies (14 hz) were performed. post-tetanic potentiation (ptp), a longer lasting form of short-term plasticity was elicited by 30 stimuli at 100hz in the presence of ap5 (d-2-amino-5-phosphonopentanoate).
Description: Mutants exhibit decrease in magnitude of the synaptic responses compared to controls.
Exp Paradigm: Synaptic strength was measured by input-output curves.
Description: Mutants exhibit decreased postsynaptic excitatory response at excitatory synapses upon presynaptic paired-pulse stimulation with long inter-stimulus intervals (greater than 100ms), compared to controls, indicating a deficit in short-term synaptic plasticity. mutants exhibit decreased paired pulse facilitation at inhibitory synapses compared to controls, measured after decreasing the neurotransmitter release probability by lowering the calcium ion concentration which converts ppd at inhibitory synapses into ppf. this indicates rims1 may have distinct functions in excitatory and inhibitory synapses.
Exp Paradigm: Synaptic responses were recorded at excitatory synapses formed by schaffer collateral/commissural fibres on ca1 pyramidal cells.
Description: Mutants exhibit decrease in prepulse inhibition compared to controls.
Exp Paradigm: Prepulse inhibition was tested at 4,6 and 8 db. ppi was measured after 4 days habituation to the acoustic chamber.
Description: Mutants spent less time freezing when exposed to the context of the foot shock, compared to controls.
Exp Paradigm: The experimental chamber is the context. freezing in response to context was measured 24 hrs, 7 and 14 days post training.
Description: Mutants show no decrease in latency to reach the hidden platform by day 11 compared to controls that show reduced latency to reach the hidden platform by day 7.
Exp Paradigm: In the hidden platform version of the water maze mice were trained using 4 trials/day for 11 days.
Description: Mutants spent an equal percentage of time in the target quadrant in which the submerged platform had been located and the quadrant opposite the platform indicating no spatial preference while controls show a marked preference for the target quadrant.
Exp Paradigm: A probe trial was performed on day 12 in which the submerged platform was removed and mice were al- lowed to swim freely for 60 s.
Description: Mutants spent less time freezing when exposed to the cue preceeding the foot shock, compared to controls.
Exp Paradigm: An auditory tone, 90 db, 2.8 khz, for 30s is the cue. freezing was measured 24 hrs post training.
Description: Mutant mice did not care for their litters even after several pregnancies, compared to controls, indicating a deficit in maternal behavior.
Exp Paradigm: NA
Description: Mutants show decreased levels of munc13-1 (unc13b) expression compared to controls. mutants show moderate decrease in munc13-3(unc13c) compared to controls.
Exp Paradigm: NA
Description: Mutants show reduction in the nmdar-mediated mepsc amplitude compared to controls.
Exp Paradigm: Recordings from ca3ca1 schaffer collateral (sc) synapses 10-15 days after virus injection.
Description: Mutants show decreased nmdar-dependent ltp in the ca1 region compared to controls.
Exp Paradigm: Recordings from ca3ca1 schaffer collateral (sc) synapses 10-15 days after virus injection.
Description: Mutants show reduction in nmdar/ampar ratio in the ca1 pyramidal neurons compared to controls.
Exp Paradigm: Recordings from ca3ca1 schaffer collateral (sc) synapses 10-15 days after virus injection.
Description: Mutants show lower input-output relationship of nmdar-mediated epscs in the ca1 pyramidal neurons compared to controls.
Exp Paradigm: Recordings from ca3ca1 schaffer collateral (sc) synapses 10-15 days after virus injection.
Description: Mutants show no change in inter-event intervals but show a rightward shift in cumulative distribution compared to controls.
Exp Paradigm: Recordings from ca3ca1 schaffer collateral (sc) synapses 10-15 days after virus injection.
Description: Mutants show significantly reduced ppf compared to controls.
Exp Paradigm: Recordings from ca3ca1 schaffer collateral (sc) synapses 10-15 days after virus injection.
Description: Mutants show no preference for the object explored earlier whereas control mice preferredthe object explored earlier to that explored last.
Exp Paradigm: Temporal order memory task is sensitive to ca1 but not ca3 disruptions.
