Lrfn2 knockout mice were shown to exhibit autism-like behavioral abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits in Morimura et al., 2017; functionally deficient LRFN2 missense variants were identified in Japanese autism and schizophrenia patients in the same report.
Molecular Function
The protein encoded by the LRFN2 gene promotes neurite outgrowth in hippocampal neurons, enhances the cell surface expression of 2 NMDA receptor subunits GRIN1 and GRIN2A, and may play a role in redistributing DLG4 to the cell periphery.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice.
Meta-analysis cohort consisted of a discovery sample of 370 ASPD cases and 5850 controls, and a replication sample of 173 cases and 3766 controls (total of 543 cases and 9616 controls)
Lrfn2 homozygous null mice exhibit decreased body weight, social interaction, social approach, mating-induced USV, expression of the presynaptic protein PSD-95, spine density in the pyramidal neurons of the hippocampal CA1 region, length of the postsynaptic density, mEPSC frequency, GluA1 in the postsynaptic density and increase social withdrawal, number of silent synapses compared to wildtype controls.
References
Type
Title
Author, Year
Primary
Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Mice with exon 2 of Lrfn2 replaced by a neo cassette. The neo cassette was removed by germline Cre recombination and heterozygous knockouts were backcrossed to C57BL/6J for six generations.
Allele Type: Knockout
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: Mutant ES Cell Line: E14
Model Source: 28604739
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Mice with exon 2 of Lrfn2 replaced by a neo cassette. The neo cassette was removed by germline Cre recombination and heterozygous knockouts were backcrossed to C57BL/6J for six generations.
Allele Type: Knockout
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: Mutant ES Cell Line: E14
Model Source: 28604739
Description: Lrfn2 knockout mice show increased expression of the nmda receptor subunit glun2a compared to controls. the number of glun2a positive puncta did not change in the hippocampus but the number of double-labelled glun2a and psd-95 puncta decreased, compared to controls. the transcript level of glun2a did not change compared to controls.
Exp Paradigm: Western blot
Description: Lrfn2 knockout mice show decreased expression of the presynaptic protein psd-95 compared to controls. lrfn2 knockout mice show no change in the transcript levels of psd-95 comapred to controls.
Exp Paradigm: Intensity and size of psd-95 positive puncta were measured.- immunohistochemistry
Description: Lrfn2 knockout mice show increased expression of the nmda receptor subunit glun2a compared to controls. the number of glun2a positive puncta did not change in the hippocampus but the number of double-labelled glun2a and psd-95 puncta decreased, compared to controls. the transcript level of glun2a did not change compared to controls.
Exp Paradigm: Quantitative pcr (qrt-pcr)
Description: Lrfn2 knockout mice show an increase in the ratio of perforated synapses to total asymmetric synapses in the ca1 radial layer of the dorsal hippocampus, compared to controls. no abnormality was detected at the presynaptic terminal.
Exp Paradigm: NA
Description: Lrfn2 knockout mice show abnormal spine morphology in the apical dendrites of dorsal ca1 pyramidal neurons in the hippocampus, comapred to controls. mutants show an increased in the number of oddly shanped spines, compared to controls. mutants show an increase in the length of the spines and a decrease in the mean width of the spine heads, compared to controls.
Exp Paradigm: NA
Description: Lrfn2 knockout mice show decreased expression of the presynaptic protein psd-95 compared to controls. lrfn2 knockout mice show no change in the transcript levels of psd-95 comapred to controls.
Exp Paradigm: Intensity and size of psd-95 positive puncta were measured.-western blot
Description: Lrfn2 knockout mice show a decrease in the length of the postsynaptic density but no change in its thickness, compared to controls.
Exp Paradigm: NA
Description: Lrfn2 knockout mice show decreased expression of the presynaptic protein psd-95 compared to controls. lrfn2 knockout mice show no change in the transcript levels of psd-95 comapred to controls.
Exp Paradigm: Intensity and size of psd-95 positive puncta were measured.- quantitative pcr (qrt-pcr)
Description: Lrfn2 knockout mice show lower failure rates at +40mv than at -70mv, comapred to controls.
Exp Paradigm: Minimal stimulation evoked ampar-epscs at -70mv and nmdar plus ampar-epscs at +40mv were recorded.
Description: Lrfn2 knockout mice show increase of ltp of field excitatory post synaptic potentials at schaffer collateral/ca1 synapses, 60 mins after tetanus, compared to controls.
Exp Paradigm: NA
Description: Lrfn2 knockout mice show an increase in the number of silent synapses comapred to controls.
Exp Paradigm: The percentage of silent synapses were calculated using the formula 1-ln(failure rate at -70)/ln(failure rate at +40).
Description: Lrfn2 knockout mice bury more marbles than controls. lrfn2 knockout mice run longer on a wheel compared to controls.
Exp Paradigm: Running wheel test
Description: Lrfn2 knockout mice bury more marbles than controls. lrfn2 knockout mice run longer on a wheel compared to controls.
Exp Paradigm: Marble-burying test
Description: Lrfn2 knockout mice exhibit a decreased prepulse inhibition of the auditory startle response compared to controls.
Exp Paradigm: A 120db acoustic stimulus was used.
Description: Lrfn2 knockout mice exhibit an enhanced startle response to an acoustic stimuli compared to controls.
Exp Paradigm: A 120db acoustic stimulus was used.
Description: Lrfn2 knockout mice frequently hid under bedding in the presence of other mice, compared to controls. this withdrawal phenotype inceased over the three days of trial.
Exp Paradigm: Three trials were carried out on 3 consecutive days.
Description: Lrfn2 knockout mice show decrease in approaching and investigating a social target, decreased social sniffing and less physical contact with a dba2 male mouse, compared to controls.
Exp Paradigm: Three trials were carried out on 3 consecutive days.
Description: Lrfn2 knockout mice show decrease in number of contacts with a caged unfamiliar mouse as well as time spent with the unfamiliar mouse compared to controls.
Exp Paradigm: Dba2 male mouse was used an the unfamiliar caged stranger in the three chamber test.
Ultrasonic vocalization: interaction induced: opposite sex stimulus1
Decreased
Description: Lrfn2 knockout male mice emitted fewer ultrasonic vocalizations when encountering an estrous female, compared to controls.
Exp Paradigm: Number, duration, and peak frequency of calls were recorded.
Description: Lrfn2 knockout mice show decrease in body weight compared to controls, in conventional group housing but not when housed individually.
Exp Paradigm: NA
Description: Lrfn2 knockout mice reach the hidden platform faster than control mice, during the second probe trial.
Exp Paradigm: Four blocks of two training trials and two probe trials were carried out, 24hrs and 48 hrs after the trianing trial.
Cued or contextual fear conditioning: memory of context: long term recall1
Increased
Description: Lrfn2 knockout mice exhibit no significant change in freezing behavior associated with contextual fear, 7 to 28 days after training, compared to controls. however, lrfn2 knockout mice discriminated between the training box and the new box more than control mice till day 7, by exhibiting a greater number of freezing responses in the trianing box than in the new box.
Exp Paradigm: The duration of the contextual fear memory retention was measured in the training box and in a box with a different texture.
Cued or contextual fear conditioning: memory of context1
Increased
Description: Lrfn2 knockout mice exhibit increase in freezing behavior associated with contextual fear, 1 hour, 1 day and 3 days after training, compared to controls.
Exp Paradigm: NA
