Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G, Yen SH, Sahara N, Skipper L, Yager D, Eckman C, Hardy J, Hutton M, McGowan E. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science. 2001 Aug 24;293(5534):1487-91. PubMed Abstract, View on AlzSWAN

REAGENTS/MATERIAL:

Double mutant mice were generated by crossing hemizygote Tg2576 3 hemizygote JNPL3. Mice were maintained on a SW/DBA2/C57B6 background.

The following tau antibodies were used: Ab39 (Yen, 1:10); Alz50 (Davies, 1:10); PHF1 (Davies, 1:100); TG3 (Davies, 1:10); CP3 (Davies, 1:100); CP13 (Davies, 1:100); PG5 (Davies, 1:100); E-1 (Yen, 1:1000); RT97 (Anderton, 1:100); AT180 (Innogenetics, 1:100); polyclonal antibody to ubiquitin, UH19 (Ksiezak-Reding, 1:500); a polyclonal antibody to amyloid-beta-crystallin (Novacastra, 1:250); an antibody to mitotic phosphoepitopes, MPM-2 (Accurate 1:200);monoclonal glial fibrillary acidic protein (GFAP) (Biogenex, 1:100); monoclonal APP (22C11) (Roche, 1:20); Conformational tau epitopes: Alz50, MC-1, and Ab39. Phosphorylated tau epitopes: RT97 (phospho-46), CP13 (phospho-202/205), CP3 (phospho-214), AT180 (phospho-231/235), TG3 (phospho-231/235), PHF-1 (phospho-396/404), and PG5 (phospho-409). Other antibodies: polyclonal E1 (human-specific tau exon 1 aa 19-33), polyclonal WKS45 antibody that recognizes mouse and human tau (aa 258-266), PHF-1 (phopho-396/404)for hyperphosphorylated tau, beta-tubulin (Sigma)and MPM-2.

ELISA sandwich using BAN50/BA27 and BAN50/BC05 for amyloid-beta 40 and 42.

FUTURE DIRECTION:
These models should allow therapies to be developed and tested that address not only amyloid deposition but also NFT formation and neuronal loss, features of AD that previous transgenic mice have failed to recapitulate.