An allelic series for studying the mouse Thoc1 gene

Thoc1 encodes an essential component of the mammalian TREX protein complex. TREX is an evolutionary conserved complex that couples elongating RNA polymerase II with RNA processing factors. Depletion of Thoc1 protein (pThoc1) compromises transcriptional elongation and nuclear export of some RNAs. Loss of Thoc1 causes periimplantation embryonic lethality in the mouse. Early embryonic lethality precludes analysis of the physiological requirements for Thoc1 in the developing embryo or adult. To circumvent this limitation, we have generated mice containing hypomorphic or conditional alleles of Thoc1. Mice homozygous for the conditional allele appear normal. Mice containing Cre recombined conditional alleles phenocopy the previously characterized Thoc1 null allele. Mice homozygous for the hypomorphic allele are viable and born at a frequency that is not significantly different from the expected Mendelian ratio. However, these mice express less pThoc1 than wild type mice and exhibit a dwarf phenotype. The dwarf phenotype can be detected in mid-gestation embryos, suggesting that Thoc1 is also required later in embryonic and postnatal development.