B6N.129S1(Cg)-Lrrc7^tm1.2Mabk/J

Stock number: 018502
Research areas: Neurobiology Research, Research Tools

Description

Densin^flox mice possess loxP sites flanking exon 3, a region encoding the transcriptional start site of the leucine rich repeat containing 7 (Lrrc7) gene, and may be useful in studying behavioral and synaptic defects associated with schizophrenia and autism spectrum disorder.

Detailed description

Densin^flox mice possess loxP sites flanking exon 3, a region encoding the transcriptional start site of the leucine rich repeat containing 7 (Lrrc7) gene. Lrrc7 encodes the scaffolding protein densin, which is involved in cell adhesion and polarity. Densin is expressed in the postsynaptic density (PSD) of the central nervous system (CNS), with some expression also seen in glomerular podocytes and sertoli cells. Homozygous mice are viable, fertile, and normal in size. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 3 deleted in cre-expressing tissues.

When crossed to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J mice (Stock No. 003724) with ubiquitous Cre recombinase expression, the surviving KO mice have deficits in short-term memory, spatial memory, prepulse inhibition, and nesting behavior similar to behaviors seen in mice with schizophrenia and autism spectrum disorder phenotypes. These densin KO mice are more anxious than wildtype mice, and males show increased aggression. Their neurons exhibit impairment of long-term depression, and alterations in glutamate receptor dynamics and spine morphology.

Development

A targeting vector was designed to insert a single loxP site upstream of exon 3, and a loxP-flanked hygromycin resistance (hygro) cassette downstream of exon 3 of the leucine rich repeat containing 7 (Lrrc7) gene. The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into 129 x C57BL/6 blastocysts and resulting chimeric males were bred with B6.FVB-Tg(EIIa-cre)C5379Lmgd/J females (Stock No. 003724). Resulting offspring contained multiple gene rearrangments; intact floxed-exon 3, intact floxed-hygro cassette, or excision of both exon 3 and the hygro cassette. Offspring containing floxed-exon 3 were bred to C57BL/6NCrl mice for at least 7 generations. Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the colony.

Allele

Symbol: Lrrc7^tm1.2Mabk
Name: targeted mutation 1.2, Mary B Kennedy
MGI accession ID: MGI:5320434
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Densin^flox; Lrrc7^flox
Marker symbol: Lrrc7
Marker name: leucine rich repeat containing 7
Marker synonyms: B230334C09Rik; densin; mKIAA1365
Chromosome: 3
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: A targeting vector was designed to insert a single loxP site upstream of exon 3, and a loxP-flanked hygromycin resistance (hygro) cassette downstream of exon 3. Cre-mediated recombination removed the hygro cassette and left exon 3 floxed.