Are you using mouse monoclonal antibodies? Heavy background staining is a common problem when your antibody was produced in the same species that your tissue sample came from. The anti-mouse secondary antibody can't distinguish between the applied mouse primary and the endogenous immunoglobulins naturally present in the mouse tissue. You can avoid this either by using a mouse-on-mouse kit, available from several vendors, or by using primariy antibodies made in other species.
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