Contribution of endogenous antibodies to learning deficits and astrocytosis in human P301S mutant tau transgenic mice

Genetic B-cell depletion from birth augmented learning deficits in tau transgenic mice

To determine a possible contribution of antibodies to phenotype and pathology of TAU58/2 mice, we first crossed them with muMT−/− mice (Fig. 1a). muMT−/− mice have a targeted disruption in transmembrane region of the Ighm gene encoding the heavy chain segment of IgM antibodies which are expressed on the surface membrane at the pre-B lymphocyte stage of cell development23. This membrane expression is required for progression from the pre-B lymphocyte stage to immature, mature and antibody-secreting plasma cell stages24. Therefore, muMT−/− homozygous mice are unable to produce B lymphocytes and antibodies. First, we confirmed the absence of antibodies and B-cells in the resulting TAU58/2.muMT−/− mice compared to TAU58/2.muMT+/+ littermates. Staining of brain sections with antibodies…

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