(A) Schematic representation of the BATKO mice. BATKO mice carry the Ucp1CreERT2 transgene, allowing the brown-adipocyte-specific expression of the tamoxifen-sensitive CreERT2 recombinase. BATKO mice are also heterozygous for the ThraAMI allele, which encodes the TRα1L400R dominant-negative receptor after Cre-mediated deletion of a STOP cassette flanked by loxP sequences. BATKO mice are homozygous for the Thrblox allele in which exon 3 is flanked by two tandem-arranged loxP sequences. After tamoxifen injection, Cre-mediated recombination selectively excise the loxP-flanked sequences in brown adipocytes, resulting in the expression of TRα1L400R and elimination of TRβ. Control mice (CTRL, not represented here) had the same genotype except for the absence of the Ucp1CreERT2 transgene and were also tamoxifen treated. (B) Sanger sequencing chromatogram of a fragment of Thra cDNA prepared from BAT RNA of BATKO mice. Arrows indicate the positions of the TRα1L400R mutations. (C) Relative mRNA expression of Thrb in different peripheral and central tissues of CTRL and BATKO mice (H: heart, M: muscle, L: liver, St: striatum, Hy: hypothalamus) (n = 5–6/group). (D) Evaluation of T3 response in propylthiouracil (PTU)-fed CTRL and BATKO mice through the induction of Hr, a well characterized TR target gene, after 24 hr of TH (+ or −; n = 5–7/group). Statistical significance is shown for the comparison of CTRL and BATKO mice treated with TH. Error bars represent the standard deviation (SD). ***p < 0.001 for the indicated comparisons.