B6;129-Anks1b^tm1Bnaj/J

Stock number: 035048
Product name: AIDA-1^fl
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

AIDA-1^fl mice have exon 20 of the ankyrin repeat and sterile alpha motif domain containing 1B (Anks1b) gene floxed. These mice may be useful when studying neurodevelopmental disorders.

Detailed description

AIDA-1^fl/fl mice have exon 20 of the ankyrin repeat and sterile alpha motif domain containing 1B (Anks1b) gene floxed. Exon 20 encodes the first exon of the phosphotyrosine-binding (PTB) domain, which is conserved across all known isoforms of the gene. These mice still contain an FRT-flanked neo cassette immediately downstream of exon 20, within the floxed region. Expressed throughout the brain, including the hippocampus, AIDA-1 is among the most abundant proteins at postsynaptic densities where it binds to the postsynaptic scaffolding protein PSD95 and associates with N-methyl-D-aspartate receptors (NMDARs). Defects in AIDA-1 have been linked to neuropsychiatric disorders, including schizophrenia, attention-deficit hyperactivity disorder, autism spectrum disorders, and speech and motor deficits. Recently, AIDA-1 has been associated with a novel neurodevelopmental disorder, ANKS1B haploinsufficiency syndrome, characterized by autism, speech deficits, hyperactivity, and sensorimotor dysfunction. Mice that are homozygous for this floxed allele are viable and fertile. Exon 20 is present in all AIDA-1 transcripts, therefore when bred to mice that express tissue-specific Cre recombinase, resulting offspring will have all known AIDA-1 splice variants deleted in the cre-expressing tissues.

When bred to Nestin-Cre mice (Stock No. 003771), expressing Cre recombinase in the central and peripheral nervous system, resulting heterozygous (Nestin-Het) offspring show small but significant sex-specific differences, with a decrease in weight, body length, and brain mass in male mice that was not significant in females. Both sexes display social deficits, hyperactivity, and sensorimotor dysfunction. Homozygous knock-out offspring (AIDA-1 Nestin Cre) are embryonic lethal.

Development

The AIDA-1^fl targeting vector was designed to insert a loxP site upstream of exon 20, and an FRT-flanked neomycin resistance (neo) cassette followed by a second loxP site downstream of exon 20 of the ankyrin repeat and sterile alpha motif domain containing 1B (Anks1b) gene. Exon 20 is the first exon encoding the phosphotyrosine-binding (PTB) domain of Anks1b. The construct was electroporated into (C57BL/6NTac x 129S6/SvEvTac)F1-derived iTL BA1 embryonic stem (ES) cells and correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric mice subsequently backcrossed to C57BL/6J mice (Stock No. 000664) for at least 20 generations by the donating laboratory (see SNP note below). 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. The FRT-flanked neo cassette is still present in the mice and has not been deleted.

In 2020, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the males sent to The Jackson Laboratory Repository. Three of the 43 markers throughout the genome were segregating with 129, on Chromosomes 1, 5, and 6, suggesting an incomplete backcross.

Allele

Symbol: Anks1b^tm1Bnaj
Name: targeted mutation 1, Bryen A Jordan
MGI accession ID: MGI:5779292
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: AIDA-1^fl
Marker symbol: Anks1b
Marker name: ankyrin repeat and sterile alpha motif domain containing 1B
Marker synonyms: AIDA-1; AIDA-1b; ANKS2; C030032C09Rik; cajalin-2; E530015N03Rik; EB1; EB-1; Gm10937; LOC380650; RGD1565556
Chromosome: 10
Strain of origin: (C57BL/6NTac x 129S6/SvEvTac)F1
Molecular note: A loxP site was inserted upstream of exon 20 (formerly designated exon 7). An FRT-flanked neomycin resistance cassette with a 3' loxP site was inserted downstream of exon 20.