Species: Mouse
Genes: MAPT, MAPT-AS1, Mapt
Modification: MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out
Disease Relevance: Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy
Strain Name: B6J.B6N-Tc(HSA17)2Mdk/J
Genetic Background: C57BL/6J
Availability: Register interest: The Jackson Laboratory, Stock No. 035398.

Summary

In these targeted replacement mice, developed by Michael Koob and colleagues at the University of Minnesota, a 190-kb region from human chromosome 17—encompassing the entire human MAPT gene—replaces the corresponding Mapt-containing region on mouse chromosome 11.

MAPT(H1.0)-GR carry the MAPT H1 haplotype. Mice carrying the H2 haplotype or H1 with the pathogenic N279K mutation are also available (see Related Strains below).

These transchromosomic lines are unique among mouse models—in addition to the entire MAPT gene, they carry MAPT-AS1, a natural antisense transcript that regulates MAPT translation (Simone et al., 2021; see May 2021 news).

MAPT(H1.0)-GR mice express human tau protein at endogenous levels, and all six tau protein isoforms are generated. MAPT-AS1 transcripts are expressed.

Homozygous mice are viable and fertile.

Modification Details

A 190-kb region from human chromosome 17—including MAPT (H1 haplotype), MAPT-AS1, and the SPPL2C sequence, which is contained within MAPT-AS1—replaced a 157-kb region on mouse chromosome 11 between, but not including, Crhr1 and Kansl1.

Related Strains

MAPT(H1.0*N279K)-GR. These transchromosomic mice carry human MAPT (H1 haplotype) with the N279K mutation and MAPT-AS1 knocked into the mouse Mapt locus. They express human tau protein at endogenous levels, and all six tau protein isoforms are generated. MAPT-AS1 transcripts are expressed. MAPT(H1.0*N279K)-GR mice are available from The Jackson Laboratory, Stock No. 035794.

MAPT(H2.1)-GR. These transchromosomic mice carry human MAPT (H2 haplotype) and MAPT-AS1 knocked into the mouse Mapt locus. They express human tau protein at endogenous levels, and all six tau protein isoforms are generated. MAPT-AS1 transcripts are expressed. MAPT(H2.1)-GR mice are available from The Jackson Laboratory, Stock No. 033668.

Phenotype Characterization

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References

News Citations

1. MIR-NATs: Noncoding RNAs That Rein in Aggregating Proteins? 22 May 2021

Research Models Citations

1. MAPT(H1.0*N279K)-GR
2. MAPT(H2.1)-GR

Paper Citations

1. Simone R, Javad F, Emmett W, Wilkins OG, Almeida FL, Barahona-Torres N, Zareba-Paslawska J, Ehteramyan M, Zuccotti P, Modelska A, Siva K, Virdi GS, Mitchell JS, Harley J, Kay VA, Hondhamuni G, Trabzuni D, Ryten M, Wray S, Preza E, Kia DA, Pittman A, Ferrari R, Manzoni C, Lees A, Hardy JA, Denti MA, Quattrone A, Patani R, Svenningsson P, Warner TT, Plagnol V, Ule J, de Silva R. MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration. Nature. 2021 Jun;594(7861):117-123. Epub 2021 May 19 PubMed.

External Citations

1. The Jackson Laboratory, Stock No. 035794
2. The Jackson Laboratory, Stock No. 033668
3. The Jackson Laboratory, Stock No. 035398

Further Reading