The invention provides compositions and methods for muting expression of an endogenous gene in an animal cell, the muting resulting from providing a muting nucleic acid to a cell. The muting nucleic acid comprises a transgene, which is substantially homologous to a portion of the endogenous gene. The portion of the endogenous gene provided on the transgene can be from the 5'-untranscribed end, from the 3' untranscribed end, from an exon or an intron in the coding portion, or from a portion that overlaps any of these portions. Methods are provided for obtaining muting nucleic acid, and for screening for molecules that can mute the gene, and for molecules that can alleviate muting of the gene.