B6J(Cg)-Lrfn2^tm1.2Csbd/Mmjax

Stock number: 032642
Product name: Lrfn2^-
Strain synonyms: SALM1 KO
Research areas: Neurobiology Research

Description

Lrfn2 (leucine rich repeat and fibronectin type III domain containing 2 or SALM1) knock-out mice may be useful for studying the regulation of excitatory synapse function, inhibitory synapse development and ultrasonic vocalization and acoustic startle behaviors.

Detailed description

Lrfn2 (leucine rich repeat and fibronectin type III domain containing 2 or SALM1) encodes a synaptic adhesion molecule involved in NMDA receptor regulation. LFRN2/SALM1 is associated with autism spectrum disorders and schizophrenia.  Exon 2 is removed in the Lrfn2 knock-out (KO) mice.  Homozygotes are viable and fertile and exhibit no observable abnormalities in the brain. Testing in the CA1 region of the Lrfn2^-/- hippocampus reveals a decrease in the frequency of inhibitory, but not excitatory synaptic transmission. However, in the medial prefrontal cortex, the frequency of excitatory synaptic transmission, but not inhibitory synaptic transmission, is decreased. In addition, inhibitory synapse density, but not length or thickness, is decreased in the CA1 pyramidal neurons as is the frequency of spontaneous inhibitory synaptic transmission. Homozygous pups separated from their mother exhibit suppressed ultrasonic vocalization. In adult homozygotes, acoustic startle is enhanced, however, other behaviors as well as learning and memory are largely unaffected. This strain may be useful for studying the regulation of excitatory synapse function, inhibitory synapse development and ultrasonic vocalization and acoustic startle behaviors.

Development

The targeting construct is composed of an FRT site, EGFP, a loxP site, a neomycin cassette, and an FRT site upstream of exon 2. A second loxP is inserted site downstream of exon 2. The construct was electroporated into C57BL/6J-693 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to Protamine-Flp mice on an unspecified background to remove the EGFP and neomycin cassette. To create the global knock-out, mice were crossed to B6Ei.129S4-Tg(Prm-cre)58Og/EiJ mice. Mice were bred to C57BL/6J for at least 8 generations.  Immunoblot analysis confirms the absence of protein in the hippocampus. Upon arrival, mice were bred to C57BL/6J inbred mice for at least one generation to establish the colony.

Allele

Symbol: Lrfn2^tm1.2Csbd
Name: targeted mutation 1.2, Eunjoon Kim
MGI accession ID: MGI:6200740
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Lrfn2
Marker name: leucine rich repeat and fibronectin type III domain containing 2
Marker synonyms: 5730420O05Rik; FIGLER2; KIAA1246; mKIAA1246; Salm1
Chromosome: 17
Strain of origin: C57BL/6J
Molecular note: The targeting construct is composed of an FRT site, EGFP, a loxP site, a neomycin cassette, and an FRT site upstream of exon 2. A second loxP is inserted site downstream of exon 2. Flp-mediated recombination removed the FRT-flanked EGFP and neo cassette leaving exon 2 floxed. Cre-mediated recombination removed exon 2. Immunoblot analysis confirms the absence of protein in the hippocampus.