Thrb^tm1Syc

Insertion of a gene targeting cassette into the gene introduced a PV mutation into exon 10, and a floxed neomycin resistance gene 1kb downstream of the polyadenylation site. Northern blot analyses indicate that expression of the mutated allele was repressed as compared to the wild-type allele. The PV mutation contains a C insertion at coding nucleotide position 1642 (codon 448) which in human patients leads to a frame shift of the carboxyl-terminal 14 amino acids of the protein and results in total loss of T3 binding and transcriptional activation. Human patients with this mutation manifest resistance to thyroid hormone (RTH). The PV mutation was originally identified in a patient with severe growth impairment. (J:65885)