C57BL/6-Psen1^{tm1.1(PSEN1)Mdk}/J

Stock number: 039177
Product name: PSEN1-GR wt
Strain synonyms: wt PSEN1-GR

Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

Humanized Psen1 (presenilin 1) wt PSEN1-GR knock-in/knock-out mice carry a 106 kb fragment of human PSEN1 gene replacing the mouse Psen1 locus. This strain maybe useful for research in Alzheimer's disease.

Detailed description

Presenilin 1 is the catalytic subunit of the gamma-secretase complex which cleaves beta-amyloid precursor protein and NOTCH receptor proteins. These humanized wildtype Psen1 knock-in/knock-out mice carry a 106 kb fragment of human PSEN1 replacing the mouse Psen1 locus. Mice homozygous for the mutation are viable and fertile with no obvious phenotype.

Development

The PSEN1-GR wt targeting vector is designed to insert a 106 kb (Chr14:73,121,400-73,227,703) fragment of the human PSEN1 (presenilin 1) in place of Chr12:83,730,110-83,793,335 of the mouse Psen1 gene on chromosome 12. The construct included a loxP-flanked neomycin selection cassette. In addition, there is also a PSEN1-DT (non-coding antisense RNA) in the human genome segment. The insertion disrupts Psen1 transcription. The construct was electroporated into C57BL/6N-PRX-B6N embryonic stem cells (ES). The neomycin cassette was removed by transient expression of Cre. Correctly targeted ES cells were injected into blastocysts. Chimeric animals were backcrossed to C57BL/6J mice for at least 5 generations prior to sending males to The Jackson Laboratory Repository in 2024. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

In 2024, 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. Four of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Psen1^{tm1.1(PSEN1)Mdk}
Name: targeted mutation 1.1, Michael D Koob
MGI accession ID: MGI:7576962
Generation method: Targeted
Attributes: Null/Knockout; Inserted expressed sequence; Humanized sequence
Synonyms: PSEN1-GR
Marker symbol: Psen1
Marker name: presenilin 1
Marker synonyms: ACNINV3; AD3; Ad3h; CMD1U; FAD; presenilin-1; PS1; PS-1; PSNL1; S182
Chromosome: 12
Strain of origin: C57BL/6NTac
Molecular note: The targeting vector is designed to insert a 106 kb (Chr14:73121400 - 73227703) fragment of the human PSEN1 in place of Chr12:83730110 - 83793335 of the mouse Psen1 gene. The construct includes a loxP-flanked neomycin selection cassette. In addition, there is also a PSEN1-DT (non-coding antisense RNA) in the human genome segment. The insertion disrupts Psen1 transcription. The neomycin cassette was removed by transient expression of Cre.