Ubiquitous expression of a cloned murine thymopoietin cDNA

Thymopoietin (TP) was originally isolated as a 5-kD 49-aa protein from bovine thymus and was subsequently observed to affect T-cell differentiation and function. We report here the molecular cloning of a murine TP cDNA. The 2,514 bp fragment contains a 630 bp open reading frame that encodes for 210 aa, highly homologous to the first 220 aa of the human TP beta and TP gamma isoforms and to bovine TP. Southern blot analysis of genomic DNA revealed that in mouse, calf and human TP is encoded by a single genomic locus. Recently, it was found that one of the TP isoforms designated TP beta is a homologous protein to the lamina-associated polypeptide 2 (LAP2), which is thought to play an important role in the regulation of nuclear architecture by binding lamin B1 and chromosomes in a manner regulated by phosphorylation during mitosis. In this study we report the TP expression at the transcription level in 17 murine and rat tissues of different origins and 18 lymphoid and nonlymphoid cell lines. The assessment of TP mRNA expression by S1-nuclease protection assays and in situ hybridizations revealed that its expression is not exclusive to thymus, but rather ubiquitous, higher in lymphatic tissues, but also in other cells characterized with a high rate of proliferation. TP was also shown to be expressed in athymic and old animals, lacking a functional thymus gland. Further in situ hybridization studies revealed that within the thymus, the highest levels of TP mRNA are noted at the cortex. These results suggest a possible role for TP in proliferation and cell cycle control.