B6J.Cg-Isr(HSA17;MAPT*S320F)1Adiuj/J

Stock number: 040796
Product name: MAPT(H1.0*)S320F-GR
Strain synonyms: MAPT(H1.0*)S320F-GR
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

MAPT(H1.0*)S320F-GR is an Alzheimer's disease model that provides the S320F variant of human MAPT in the humanized Isr(HSA17)2Mdk model, which replaced the mouse Sppl2c and Mapt with wildtype human sequence for those genes.

Detailed description

This Alzheimer's disease model has a mutation in the humanized Isr(HSA17)2Mdk model. Isr(HSA17)2Mdk replaces the mouse Sppl2c and Mapt with wildtype human sequence for those genes. The MODEL-AD team at The Jackson Laboratory subsequently CRISPR/Cas9 modified this to have an S320F variant in the human MAPT sequence, yielding Isr(HSA17;MAPT*S320F)1Adiuj. The S320F variant has been associated with accelerated Beta-amyloid deposition, Frontotemporal Dementia, and Pick's disease. This mouse strain is currently being phenotypically assessed. This mouse strain is currently being phenotypically assessed [August 2025]. If additional characterization of these mice is performed, we may modify the strain description accordingly.

Development

The humanized Isr(HSA17)2Mdk substitution was generated in C57BL/6NTac and crossed with other strains to generate B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Isr(HSA17)2Mdk App^em1Adiuj/J (the LOAD3 model; Stock No. 037778). This was modified by The Jackson Laboratory MODEL-AD program by CRISPR/Cas9-mediated point substitution of the human MAPT sequence in Isr(HSA17)2Mdk to have a non-coding C-to-T (rs63751011) substitution at position 44,087,784 (GRCh37/hg19) in intron 10. The resulting mutant founder was bred two generations to B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Isr(HSA17)2Mdk App^em1Adiuj/J after which crosses were done to C57BL/6J to eliminate the Apoe^{tm1.1(APOE*4)Adiuj} and App^em1Adiuj alleles, generating this strain with just the Isr(HSA17;MAPT*S320F)1Adiuj mutant humanized sequence.

Allele

Symbol: Isr(HSA17;MAPT*S320F)1Adiuj
Name: interspecies replacement, human Chr 17, MODEL-AD Center 1
MGI accession ID: MGI:8220230
Generation method: Endonuclease-mediated
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Isr(HSA17;MAPT*S320F)1Adiuj
Marker name: interspecies replacement, human Chr 17, MODEL-AD Center 1
Chromosome: 11
Strain of origin: B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Isr(HSA17)2Mdk App^em1Adiuj/J
Molecular note: Isr(HSA17)2Mdk replaced 157 kb of mouse Chromosome 11 stretching from, but not including, Crhr1 to Kansl1, with 190 kb of syntenic sequence from human Chromosome 17, which replaced mouse Sppl2c (signal peptide peptidase 2C) and Mapt (microtubule-associated protein tau) genes with human SPPL2C and MAPT (H1 haplotype) genes. The MODEL AD team at The Jackson Laboratory subsequently CRISPR/cas9 modified the inserted human MAPT sequence in Isr(HSA17)2Mdk to have a non-coding C to T (rs63751011) substitution at position 44087784 (GRCh37/hg19) in intron 10. This dominant mutation is identified in early onset frontotemporal dementia (FTD) patients.