| Summary: | Thermogenesis plays an important role in the survival of sheep exposed to low temperatures; however, little is known about the genetic mechanisms underlying cold adaptation in sheep. We examined 6 Altay (A) and 6 Hu (H) six-month-old ewe lambs. Altay sheep are raised in northern China and are adapted to dry, cold climates, while Hu sheep are raised in southern China and are adapted to warm, humid climates. Each breed was divided into two groups: chronic cold sheep, exposed to −5 °C for 25 days (3 A<sup>c</sup>; 3 H<sup>c</sup>), and thermo-neutral sheep, maintained at 20 °C (3 A<sup>w</sup>; 3 H<sup>w</sup>). The transcriptome profiles of hypothalamus, tail-fat and perirenal fat tissues from these four groups were determined using paired-end sequencing for RNA expression analysis. There are differences in cold tolerance between Hu and Altay sheep. Under cold exposure of the lambs: (1) UCP1-dependent thermogenesis and calcium- and cAMP-signaling pathways were activated; and (2) different fat tissues were activated in Hu and Altay lambs. Several candidate genes involved in thermogenesis including <i>UCP1</i>, <i>ADRB3</i>, <i>ADORA2A</i>, <i>ATP2A1</i>, <i>RYR1</i> and <i>IP6K1</i> were identified. Molecular mechanisms of thermogenesis in the sheep are discussed and new avenues for research are suggested.
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