B6;129-Nrxn3^tm4.1Sud/J

Stock number: 016194
Product name: NS4
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

These NS4 mutant mice possess loxP sites flanking exon 20 (alternative splice site 4) of the neurexin III (Nrxn3) gene, and a mutated exon 20 splice acceptor sequence. This strain may be useful for studying neuronal synapses related to alcoholism, dependence, and addiction behaviors.

Detailed description

These NS4 mutant mice possess loxP sites flanking exon 20 (alternative splice site 4) of the neurexin III (Nrxn3) gene, and a mutated exon 20 splice acceptor sequence. Mice that are homozygous for this allele are viable, fertile, and normal in size. NRXN3, an intercellular cell signaling protein, is expressed in neurons involved in addictive behaviors and is associated with nicotine and opioid dependence and substance abuse. Nrxn3 has two distinct promoters and five alternative splice sites. These Nrxn3 mice always incorporate alternative splice site 4 in the transcript. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have this mutated exon 20 deleted in the cre-expressing tissues. This strain may be useful for studying neuronal synapses related to alcoholism, dependence, and addiction behaviors.

Development

A targeting vector was designed to insert a loxP site upstream of exon 20 (alternative splice site 4) followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 20 of the neurexin III (Nrxn3) gene. The splice acceptor sequence of exon 20 (TGTTTTTTAAACTTTAAAG) was substituted with a generic one (TGTTTTTTCGTCTTCCTAG) to make the exon always incorporated in the transcript. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl<+>-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred. Offspring, were bred with Flp transgenic mice on a mixed C57BL/6:129 background to delete the neo cassette. The resulting progeny were crossed to remove the Flp-expressing transgene. These NS4 mice were maintained on a mixed background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Nrxn3^tm4.1Sud
Name: targeted mutation 4.1, Thomas C Sudhof
MGI accession ID: MGI:4946102
Generation method: Targeted
Attributes: Modified isoform(s)
Marker symbol: Nrxn3
Marker name: neurexin III
Chromosome: 12
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A targeting vector was designed to insert a loxP site upstream of exon 20 (alternative splice site 4) followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 20. The less common splice acceptor sequence of exon 20 (TGTTTTTTAAACTTTAAAG) was substituted with a much more common one (TGTTTTTTCGTCTTCCTAG) to make the exon always incorporated in the transcript.