Upstairs to downstairs shouldn't be a problem; I was thinking of something more along the lines of using wireless to cross an open space where the direct line from A to B was open to the elements. (Rain dampens the radio waves.) Radio propagation can be awfully weird, though!

If you're having problems downstairs on a wired connection, your wifi is pretty much exonerated.

I don't see how rain could affect a wireless mouse (well, as long as you keep it dry, obviously).