Thoc1 functions in mouse development, reproduction and tumorigenesis Free

1998

Thoc1 is a transcription elongation factor that was recently identified as a potential prognostic marker for breast cancer, linking transcriptional elongation and mRNA export to metastatic breast cancer. To address the physiological function of Thoc1, we have constructed a Thoc1 hypomorphic allele expressing decreased levels of Thoc1 protein in all tissues examined. Mice homozygous for the hypomorphic allele (H allele) are viable. However, Thoc1 hypomorphic mice exhibit dwarfism that is independent of IGF-1 and growth hormone levels. We also find that Thoc1 hypomorphic mice display dramatic defects in the development and function of the reproductive system. Male Thoc1H/H mice are infertile. The testes are small with a severe deficiency in the number of mature sperm. Germ cells appear to arrest in meiosis blocking subsequent gametogenesis. Thoc1H/H female mice are subfertile, in part because of reduced numbers of follicles. Interestingly, we also observe increased incidence of thymic lymphoma in Thoc1H/H mice. These in vivo findings suggest a critical role for Thoc1 in development, reproduction, and tumorigenesis.