Thyroid hormone receptor alpha (TR alpha), a NR1 Thyroid Hormone-Like Receptor, mediates the diverse actions of thyroid hormone in development, differentiation, and metabolism. Four protein isoforms are encoded by the same TR alpha genomic locus: TR alpha1 (410 aa) (Nakai et al. 1988), TR alpha2 (490 aa) (Nakai et al. 1988), TR deltaalpha1 (~154 aa), and TR deltaalpha2 (~237 aa), however, only TR alpha1 is able to bind the ligand (Lazar et al. 1988). TR alpha1 and TR alpha2 are products of alternative splicing of the primary TR alpha mRNA, whereas TR deltaalpha1 and TR deltaalpha2 arise from transcription of an internal promoter in intron 7 of the TR alpha gene. A truncated form of TR alpha, called p43 for 43- kDa, has been shown to regulate mitochondrial transcription Casas et al. 2003. Mice lacking all forms of TR alpha have been shown to be viable, but show reduced linear growth, delayed bone maturation, increased hypothermia, reduced thickness of the intestinal mucosa, lowered heart rates, and lowered serum T4. TR alpha has been linked to chronic fatigue Englebienne et al. 2003.