MAPT(H2)-GR mice express the human MAPT (H2 haplotype) and MAPT-AS1 transcripts and the typical MAPT protein isoforms.
Michael Koob, University of Minnesota
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) and MAPT-AS1 transcripts and the typical MAPT protein isoforms.
A 157 kb deletion on mouse chromosome 11 stretching from, but not including, Crhr1 to Kansl1 is replaced by a syntenic 190 kb region from human chromosome 17 (HSA17). In this transchromosomal (Tc) strain, the mouse Sppl2c (signal peptide peptidase 2C) and Mapt (microtubule-associated protein tau) genes are replaced by human SPPL2C and MAPT (H2 haplotype) genes. The deletion/insertion was made using C57BL/6N-PRX-B6N embryonic stem cells (ES) and loxN-flanked hygromycin resistance cassette. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to B6.Cg-Edil3Tg(Sox2-cre)1Amc/J (Stock No. 008454) to remove the hygro cassette and then backcrossed to C57BL/6J for at least 5 generations. The Cre transgene was removed by breeding. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||transchromosomal, human 17, line 1, Michael Koob|
|Allele Type||Targeted (Inserted expressed sequence, Humanized sequence)|
|Gene Symbol and Name||Tc(HSA17)1Mdk, transchromosomal, human 17, line 1, Michael Koob|
|Strain of Origin||C57BL/6NTac|
|Molecular Note||A 157 kb deletion on mouse chromosome 11 stretching from, but not including, Crhr1 to Kansl1 is replaced by a syntenic 190 kb region from human chromosome 17 (HSA17). In this transchromosomal (Tc) strain, the mouse Sppl2c (signal peptide peptidase 2C) and Mapt (microtubule-associated protein tau) genes are replaced by human SPPL2C and MAPT genes and a loxN-flanked hygromycin cassette. Cre-mediated recombination removed the hygromycin cassette.|
When maintaining a live colony, these mice are bred by homozygote sibling matings.
When using the MAPT(H2)-GR mouse strain in a publication, please cite the originating article(s) and include JAX stock #033668 in your Materials and Methods section.
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