GLP-1: a novel zinc finger protein required in somatic cells of the gonad for germ cell development.
Mouse gonadal development is regulated by a variety of transcription factors. Here we report the identification and characterization of a novel nuclear zinc finger protein called GATA like protein-1 (GLP-1), which is expressed at high levels in the somatic cells of the developing gonads, including Leydig cells in the testes and granulosa cells in the ovaries. Biochemical analysis of GLP-1 shows that it acts as a transcriptional repressor of GATA factor function. To determine the necessity of GLP-1 in gonadal development, a null allele in mice was generated by replacing all of the coding exons with the bacterial lacZ gene. GLP-1(lacZ) null mice are viable with no detectable defects in visceral organ development; however, both males and females are completely infertile. Loss of GLP-1 leads to defective sperm development in males with a marked reduction in mature spermatids observed as early as postnatal week 1. In females, loss of GLP-1 leads to a severe block in germ cell development as early as E17.5. Together, these data identify GLP-1 as a critical nuclear repressor in somatic cells of the gonad that is required for germ cell development, and highlight the importance of somatic-germ cell interactions in the regulation of this critical process.
Li
Shanru
S
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lu
Min Min
MM
Zhou
Deying
D
Hammes
Stephen R
SR
Morrisey
Edward E
EE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D050982:GATA1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005854:Germ Cells / Q000254:growth & development*; D007150:Immunohistochemistry; D007763:Lac Operon; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse