B6.Cg-App^em1Adiuj/J

Stock number: 033013
Product name: B6J hAbeta
Research areas: Neurobiology Research, Research Tools

Description

This B6J hAbeta mutant strain carries a CRISPR/Cas9-generated App allele with a humanized Abeta1-42 region (G601R, F606Y, R609H in the mouse gene, corresponding to amino acid positions 676, 681, 684 in the human APP locus). These mice may be suitable for use in studies related to Alzheimer's disease.

Detailed description

This hAbeta mutant strain carries a mutant allele of the App gene containing G601R, F606Y, and R609H point mutations. The targeted App gene encodes amyloid beta precursor protein, a transmembrane cell surface receptor that is cleaved by secretases. Mutations in this gene have been associated with Alzheimer's disease.

Both heterozygous and homozygous mice are viable and fertile (March 2020). If additional characterization of these hAbeta mice is performed, we may modify the strain description accordingly.

Development

This mutant line was generated by breeding the Apoe^{tm1.1(APOE*4)Adiuj} and Trem2^em1Adiuj/J alleles out of Stock No. 030670.



Important note about App isoforms and exon numbering: The App-201 isoform (695 aa protein) is encoded by 16 exons, of which the Abeta sequence is encoded by exon 14. The App-206 isoform (770 aa protein) is encoded by 18 exons, of which the Abeta sequence is encoded by exon 16.

Allele

Symbol: App^em1Adiuj
Name: endonuclease-mediated mutation 1, MODEL-AD Center
MGI accession ID: MGI:6164022
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Marker symbol: App
Marker name: amyloid beta (A4) precursor protein
Chromosome: 16
Strain of origin: B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Trem2^em1Adiuj/J
Molecular note: CRISPR/Cas9 genome editing methodologies are used to introduce G601R, F606Y, and R609H point mutations into the App gene. G601R corresponds to a GGA to CGA nucleotide change, F606Y represents a TTT to TAT change, and R609H incorporates a CGC to CAT nucleotide change.