The homeo box is a 180 base pair protein coding sequence that is a component of several Drosophila homeotic and segmentation genes. The subsequent identification of homeo box sequences in mammals raises the provocative possibility that at least some of the genes that control mammalian development are in hand. We have identified a new mouse homeo box gene called MH-3. The pattern of expression of the MH-3 gene is intriguing: a) in the adult mouse, this gene is expressed specifically in the testis or ovary b) in the adult testis, this gene is expressed in germ cells at late meiotic stages c) during embryogenesis, the expression of this gene was detected at stages that precede gonadal and sexual differentiation. We will study the MH-3 homeo box gene with respect to its structure and expression and function in meiosis and embryogenesis. 1. The temporal and spatial control of MH-3 gene expression will be analyzed in detail in adult gonads and in mouse embryos by in situ hybridization and indirect immunoflouresence, using specific MH-3 nucleic acid and antibody probes. 2. The MH-3 gene will be isolated and characterized. Cis acting sequences that control the specificity of expression will be studied using hybrid genes in transgenic mice. 3. Loss of MH-3 gene function will be attempted in embryos by microinjecting antisense DNA constructs, antisense RNA or antibodies into fertilized mouse eggs. The embryonic and postnatal development of the manipulated embryos will be studied after transfer into pseudopregnant recipients. 4. To ask whether MH-3 proteins are essential for meiosis, this process will be analyzed in primary oocytes microinjected with antibodies and in spermatogenic cell cultures infected with recombinant retroviruses expressing the MH-3 antisense RNA.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Schools of Medicine
Los Angeles
United States
Zip Code
Kundu, R K; Sangiorgi, F; Wu, L Y et al. (1999) Expression of the human immunodeficiency virus-Tat gene in lymphoid tissues of transgenic mice is associated with B-cell lymphoma. Blood 94:275-82
Tan, H; Ransick, A; Wu, H et al. (1998) Disruption of primary mesenchyme cell patterning by misregulated ectodermal expression of SpMsx in sea urchin embryos. Dev Biol 201:230-46
Kundu, R K; Sangiorgi, F; Wu, L Y et al. (1998) Targeted inactivation of the coagulation factor IX gene causes hemophilia B in mice. Blood 92:168-74
Wu, L; Wu, H; Ma, L et al. (1997) Miz1, a novel zinc finger transcription factor that interacts with Msx2 and enhances its affinity for DNA. Mech Dev 65:3-17
Ma, L; Swalla, B J; Zhou, J et al. (1996) Expression of an Msx homeobox gene in ascidians: insights into the archetypal chordate expression pattern. Dev Dyn 205:308-18
Ma, L; Golden, S; Wu, L et al. (1996) The molecular basis of Boston-type craniosynostosis: the Pro148-->His mutation in the N-terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences. Hum Mol Genet 5:1915-20
Lazik, A; Liu, Y; Bringas, P et al. (1996) A sensitive method for analyzing beta-galactosidase reporter gene expression in tissue sections of mouse embryos. Trends Genet 12:445-7
Liu, Y H; Ma, L; Kundu, R et al. (1996) Function of the Msx2 gene in the morphogenesis of the skull. Ann N Y Acad Sci 785:48-58
Liu, Y H; Kundu, R; Wu, L et al. (1995) Premature suture closure and ectopic cranial bone in mice expressing Msx2 transgenes in the developing skull. Proc Natl Acad Sci U S A 92:6137-41
Liu, Y H; Ma, L; Wu, L Y et al. (1994) Regulation of the Msx2 homeobox gene during mouse embryogenesis: a transgene with 439 bp of 5' flanking sequence is expressed exclusively in the apical ectodermal ridge of the developing limb. Mech Dev 48:187-97

Showing the most recent 10 out of 17 publications