The T/t complex on mouse chromosome 17 which includes the major histocompatibility complex (MHC), also contains a number of mutant gene that affect the differentiation of spermatozoa, and others that function during early embryonic development. Thus, it has been intensively investigated as model system for analyzing both immunobiology and differentiation, and their genetic control. Until recently, however, the molecular biology of the tau-complex was limited to chromosomal walking, marker identification, and random screening. This phase has now been accomplished. New results from this laboratory, obtained with a combination of genetic and molecular techniques have shown that the MHC has become the site major interest in the tau-complex and provided the tools to investigate a gene complex that regulates development in a mammal. Five out of six newly cloned male germ-cell-expressed genes residing in the MHC show expression changes in wild type versus tau-mutant testis. In terms of early embryo development, of the four recessive, early embryo tau-lethal genes interspersed with MHC genes , two have been more precisely located: tw5 is genetically inseparable from H-2K, and one of the earliest acting mammalian lethals, t12, is located either in the TL region or the uncloned """"""""gap"""""""" between the TL and Qalpha regions. The early-embryo expressed transcription factor, Oct-4, has also been mapped to the gap between TL and Qalpha, and preliminary studies indicate it may well be t12. This project proposes three complementary strategies to define the molecular and biological function of these interesting tau-complex genes. (1) Analyze the cloned testis-expressed genes at the transcriptional, translational, and protein level. Ultimately, we will employ transgenic technology to study their dominant function. (2) Identify and map cloned genes, both from our laboratory and others, that are transcribed from within the tau-complex, and expressed in early mouse embryos. We will concentrate on those that are candidates for the tau-lethal mutation. Currently, this includes Oct-4 and six other early embryonic tau/tau complex encoded cDNAs. (3) Recombinational genetic analysis of the tau/tau complex region to support the molecular and functional analysis. Our long- term objective is to understand the molecular mechanisms and genetic control of cellular commitment.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Immunobiology Study Section (IMB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Austin
Schools of Arts and Sciences
United States
Zip Code
Pike, Schuyler T; Rajendra, Rashmi; Artzt, Karen et al. (2010) Mitochondrial C1-tetrahydrofolate synthase (MTHFD1L) supports the flow of mitochondrial one-carbon units into the methyl cycle in embryos. J Biol Chem 285:4612-20
Wu, Jiang I; Centilli, M A; Vasquez, Gabriela et al. (2007) Tint maps to mouse chromosome 6 and may interact with a notochordal enhancer of Brachyury. Genetics 177:1151-61
Wu, Jiang I; Rajendra, Rashmi; Barsi, Julius C et al. (2007) Targeted disruption of Mib2 causes exencephaly with a variable penetrance. Genesis 45:722-7
Barsi, Julius C; Rajendra, Rashmi; Wu, Jiang I et al. (2005) Mind bomb1 is a ubiquitin ligase essential for mouse embryonic development and Notch signaling. Mech Dev 122:1106-17
Wu, Jiang I; Reed, Robyn B; Grabowski, Paula J et al. (2002) Function of quaking in myelination: regulation of alternative splicing. Proc Natl Acad Sci U S A 99:4233-8
Saccomanno, L; Loushin, C; Jan, E et al. (1999) The STAR protein QKI-6 is a translational repressor. Proc Natl Acad Sci U S A 96:12605-10
Wu, J; Zhou, L; Tonissen, K et al. (1999) The quaking I-5 protein (QKI-5) has a novel nuclear localization signal and shuttles between the nucleus and the cytoplasm. J Biol Chem 274:29202-10
Venables, J P; Vernet, C; Chew, S L et al. (1999) T-STAR/ETOILE: a novel relative of SAM68 that interacts with an RNA-binding protein implicated in spermatogenesis. Hum Mol Genet 8:959-69
Vernet, C; Abe, K; Artzt, K (1998) Genetic mapping of 10 microsatellites in the t complex region of mouse chromosome 17. Mamm Genome 9:472
Rennebeck, G; Lader, E; Fujimoto, A et al. (1998) Mouse Brachyury the Second (T2) is a gene next to classical T and a candidate gene for tct. Genetics 150:1125-31

Showing the most recent 10 out of 38 publications