The humanized 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 CGG-to-tGG codon change that resulted in the phenotypic R406W point substitution, and this was accompanied with silent sequence changes CTCAGC-to-CTtAGt in L408 S409 codons to facilitate mutagenesis. The human R406W variant is associated with tauopathy of both frontotemporal lobar degeneration and early-onset memory loss and Alzheimer's disease-like symptoms (PMID:36171642). Patients with this variant have been found to have increased tau p217 phosphorylation but normal amyloid beta 42/40 ratios in cerebrospinal fluid (PMID:34342183). 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.

The use of this mouse model is subject to the terms and conditions of the Limited Use Label License from Caribou Biosciences, Inc.

The use of this mouse strain or other product (the "Licensed Product") is subject to the terms and conditions of the Limited License from The Broad Institute.

MAPT(H1.0*)R406W-GR is an Alzheimer's disease model that provides the R406W 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.

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