Multiple sequences encoding potential thyroid hormone receptors isolated from mouse skeletal muscle cDNA libraries

Several groups have isolated cDNA clones encoding different thyroid hormone binding proteins, although in each case only one type of cDNA was characterized for a given tissue (1-5). We have found three different cDNAs in libraries prepared from mouse skeletal muscle tissue at different stages of development and from the mouse C2 muscle cell line. Two different probes were used to screen these libraries: a 500 bp Pstl fragment from a human c-erbA cDNA clone and a 1.2 kb BamHI-Pstl fragment from a rat pituitary cell cDNA (see ref. 5). DNA sequence analysis of the mouse cDNAs suggests that they arise from the same gene since all the common regions are identical. However, these cDNAs differ near the 3' end of the coding region where putative splice sites have been identified from consensus sequences, AAG/G or CAG/G (6) (underlined). The cDNA isolated from the C2 cell line library is homologous to the chicken embryonic cDNA (1) and the rat brain cDNA (3); it is called o1. The second cDNA (ending at an internal EcoRI site), isolated from an adult muscle cDNA library, is homologous to the human testicular cDNA (3) and is called oc2. The third cDNA (also ending at an EcoRI site), isolated from a neonatal muscle cDNA library, appears to result from alternative splicing of sequences from the a2 cDNA; this new sequence is called a3. The coding sequence of oc1 is presented below, and the a2 and cc3 sequences are shown beginning at nucleotide 1081. These data suggest that at least three different potential thyroid hormone receptors are formed by alternative splicing. They may be expressed at different times during muscle development.