International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

I26. GPBOX, A Homeobox Gene Preferentially Expressed in Female Germ Cells at the Onset of Sexual Dimorphism in Mice

Nobuyoshi Takasaki, Robert McIsaac, Tracy Rankin and Jurrien Dean
Laboratory of Cellular and Developmental Biology, NIDDK, NIH

Mouse gestation takes place over 20 days and undifferentiated gonads are first detected as part of the urogenital ridges at embryonic day 10 (~E10). Although either XY or XX germ cells can be diverted from their normal development in the presence of somatic cells from the opposite sex, they rarely complete gametogenesis and are mostly infertile as adults. Thus, germ cells must express gene products required for successful, gender-specific development of eggs and sperm. To identify such products, sex-specific urogenital ridge cDNA libraries were constructed from E12-13 mouse embryos. After mass excision and isolation of plasmid DNA, approximately 4800 expressed sequence tags were determined and compared to existing databases. Few cDNA were specifically expressed in the urogenital ridge, but one, designated GPBOX (Germ-line-Placenta-homeoBOX), encodes a 227 amino acid homeobox protein that is first detected at E10.5 in embryos as well as in the extraembryonic placenta. The Gpbox gene is single copy in the mouse genome and located on the X chromosome in close proximity to a highly homologous gene, Psx1. Within the embryo, the expression of Gpbox is limited to the gonad, and transcripts are not detected in adult tissues. Although comparable levels are initially present in both sexes, GPBOX transcripts accumulate faster in female germ cells and peak at E12.5 where they are present in 5-fold greater abundance than in males. The persistence of GPBOX transcripts in females germ cells until E15.5 and their virtual disappearance in males by E13.5 suggest that Gpbox may play a role in mammalian oogenesis. To further investigate the function of this homeodomain protein, mouse lines lacking GPBOX have been established by targeted mutagenesis. Homozygous null Gpbox females and hemizygous null males are normal at birth with unremarkable gonadal histology. These results raise the possibility that Psx1, a co-expressed closely linked gene that encodes a homeobox protein 82% identical to GPBOX may provide redundancy. Thus, mouse lines with null mutations in both Gpbox and Psx1 are now being established to further investigate the role of these germ-cell homeobox genes in germ cell development.

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