B6(Cg)-Baiap2^tm1.1Csbd/J

Stock number: 038903
Product name: Irsp53^fl
Research areas: Neurobiology Research, Research Tools

Description

Irsp53^fl mice have loxP sites flanking exons 4-6 of the Baiap2 gene. This strain may be useful for studying excitatory and inhibitory neurons distinct impacts on behaviors and synaptic transmission.

Detailed description

Brain-specific angiogenesis inhibitor 1-associated protein 2 (Baiap2) encodes IRSp53, an excitatory postsynaptic scaffolding protein expressed in excitatory neurons in the neocortex and GABAergic neurons in the striatum and cerebellum. It regulates dendritic spines and synaptic function through its ability to coordinate GTPase-dependent modulation of actin filaments. IRSp53 has been implicated in defects in behavioral and social interaction in autism spectrum disorders (ASD), schizophrenia, and attention deficit/hyperactivity disorder (ADHD).

This strain has loxP sites flanking exons 4-6. Mice that are homozygous for this allele are viable and fertile and have no overt phenotype. They express normal Irsp53 levels. The donating investigator reports that they did not check for EGFP expression by immunohistochemistry or Western blot. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 4-6 removed in the cre-expressing tissues of the offspring.

When bred to Emx1-Cre mice (Stock No. 005628), homozygous IRSp53 deletion in excitatory neurons leads to strong social deficits and hyperactivity without affecting anxiety-like behavior in male mice. This deletion in male mice also induces an increased ratio of evoked excitatory and inhibitory synaptic transmission (E/I ratio) in layer V pyramidal neurons in the prelimbic region of the medial prefrontal cortex (mPFC), whereas the same mutation does not alter the E/I ratio in female neurons. Excitatory neuronal IRSp53 deletion in females induces hyperactivity and moderate social deficits with unaltered cortical E/I ratio.

When bred to Viaat-Cre mice (Stock No. 017535), homozygous IRSp53 deletion in inhibitory GABAergic neurons has minimal impacts on social interaction, locomotor activity, or anxiety-like behavior.

Development

A targeting vector was designed to contain (from 5' to 3') a frt site, an En2 splice acceptor, an internal ribosome entry site (IRES) fused to an EGFP sequence with a polyadenylation signal, and a floxed cassette containing a neo and a second frt site all upstream of exon 4 of the brain-specific angiogenesis inhibitor 1-associated protein 2 (Baiap2) gene. A third loxP was placed downstream of exon 6. The construct was electroporated into C57BL/6J-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting Irsp53^fl mice with the frt-flanked cassette and all three loxP sites intact, were bred to Prm1-flp mice on a C57BL/6J background to remove the frt-flanked cassette and the 5' loxP site, leaving exons 4-6 floxed. Mice were further maintained on a C57BL/6J genetic background (Stock No. 000664). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Baiap2^tm1.1Csbd
Name: targeted mutation 1.1, Eunjoon Kim
MGI accession ID: MGI:7536957
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Reporter
Synonyms: Irsp53^fl
Marker symbol: Baiap2
Marker name: brain-specific angiogenesis inhibitor 1-associated protein 2
Marker synonyms: BAP2; DEE120; FLAF3; IRSp53; WAML
Chromosome: 11
Strain of origin: C57BL/6J
Molecular note: A targeting vector is designed to contain (from 5' to 3') a frt site, an En2 splice acceptor, an internal ribosome entry site (IRES) fused to an EGFP sequence with a polyadenylation signal, and a floxed cassette containing a neo and a second frt site all upstream of exon 4. A third loxP was placed downstream of exon 6. Flp-mediated recombination removed the neo cassette and the 5' loxP site, leaving exons 4-6 floxed.