Abi3S209F is a CRISPR/Cas9-generated mutant of the ABI family member 3 (Abi3) gene carrying the S212F mutation that corresponds to the human S209F SNP associated with increased risk of sporadic Alzheimer's disease. These mice may be useful in pre-clinical studies of AD.
Dr. Grant MacGregor, University of California, Irvine
To create the Abi3S209F allele, CRISPR/Cas9 endonuclease-mediated genome editing of Abi3 was used to introduce a S212F mutation. This mutant allele models a SNP (rs616338) found in human ABI3 that encodes a missense mutation associated with increased risk of sporadic Alzheimer's disease. The mechanism of action of ABI3 is not yet fully understood. It appears to function in regulation of actin cytoskeletal dynamics, in a manner distinct from its related family members ABI1 and ABI2. If additional characterization of these Abi3S209F mice is performed, we may modify the strain description accordingly.
RNA-seq analysis of hippocampus and cortex indicates that the Abi3em1Aduci allele is expressed at a level similar to the wild-type Abi3 allele, with no evidence of cryptic splicing products from the mutant allele.
Both heterozygous and homozygous mice are viable and fertile.
Guide RNA (CCCTGCCGAGGCCAAGGAAG) was designed to create an TCT to TTC missense mutation resulting in a serine to phenylalanine change (S212F) in the ABI family member 3 (Abi3) gene. This mutation (SNP rs616338) is homologous to the human S209F SNP which has been shown to correlate with increased risk of sporadic Alzheimer's disease. One silent DNA mutation was also introduced. The crRNA, tracrRNA and CAS9 nuclease were complexed to form an RNP, then introduced into the cytoplasm of C57BL/6J-derived zygotes with well recognized pronuclei. Surviving embryos were transferred to pseudopregnant females. Progeny were screened by DNA sequencing to identify correctly targeted pups, which were then bred to C57BL/6J mice (Stock No. 000664) for germline transmission. The Abi3S209F colony was backcrossed to C57BL/6J for a total of at least two generations. 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 Name||endonuclease-mediated mutation 1, Frank LaFerla|
|Allele Type||Endonuclease-mediated (Humanized sequence)|
|Gene Symbol and Name||Abi3, ABI gene family, member 3|
|Strain of Origin||C57BL/6J|
|Molecular Note||CRISPR/cas9 genome editing is used to create an TCT to TTC missense mutation resulting in a serine to phenylalanine change (S212F). This mutation (SNP rs616338) is homologous to the human S209F SNP which has been shown to correlate with increased risk of sporadic Alzheimer's disease. One silent DNA mutation was also introduced.|
When maintaining a live colony, homozygous mice may be bred together.
When using the Abi3*S209F mouse strain in a publication, please cite the originating article(s) and include JAX stock #035871 in your Materials and Methods section.