The transchromosomal (Tc) MAPT(H2)-GR mice contain a syntenic 190 kb region from human chromosome 17 (HSA17) that includes SPPLC2 (signal peptide peptidase 2C) and MAPT (microtubule-associated protein tau), specifically the H2 haplotype. The region replaces 157 kb on mouse chromosome 11 stretching from, but not including, Crhr1 to Kansl1. The SPPL2C sequence is included because it is embedded entirely in the MAPT-AS1 transcribed region.
Human MAPT (microtubule-associated protein tau) is found within a 900 kb inversion on Chr 17q21 that defines two haplotypes, H1 and H2, found in Caucasians. The haplotypes are distinguished by a series of polymorphisms that include the MAPT sequence. A227A (GCA to GCG), is a silent point mutation in exon 9 of the MAPT isoform 441. The minor G allele is carried by H2 and the A allele is found in the more common H1 haplotype. H1 is linked with late onset Alzheimer's disease (AD) risk, progressive supranuclear palsy, Parkinson's disease, and corticobasal degeneration. H2 is associated with decreased risk of late onset AD, and lower MAPT levels in the cerebellum and temporal cortex.
Homozygous mice are viable and fertile and exhibit no obvious phenotype. These mice express the human MAPT (H2 haplotype), MAPT-AS1 transcripts and the typical MAPT protein isoforms. A modified H1 haplotype carrying the pathogenic N279K mutation is distributed as Stock No. 035794. The H1 haplotype is distributed as Stock No. 035398 C57BL/6-Tc(HSA17)2Mdk/J. MAPT IVS10+16 C>T mice, distributed as Stock No. 036664, express the H1 haplotype and contain a non-coding C to T (rs63751011) mutation in intron 10.
