Complex phenotype of mice homozygous for a null mutation in the Sp4 transcription factor gene

Background: Sp4 is a zinc finger transcription factor which is closely rela ted to Spl and Sp3. All three proteins recognize the same DNA elements and can act as transcriptional activators through glutamine-rich activation dom ains. Unlike Spl and Sp3, which are ubiquitous proteins, Sp4 is highly abun dant in the central nervous system, but also detectable in many other tissu es. Results: We have disrupted the mouse Sp4 gene by a targeted deletion of the exons encoding the N-terminal activation domains. Sp4 knockout mice show a complete absence of Sp4 expression. They develop until birth without obvio us abnormalities. After birth, two-thirds die within 4 weeks. Surviving mic e are growth retarded. Male Sp4(null) mice do not breed. The cause for the breeding defect remains obscure since they show complete spermatogenesis. I n addition, pheromone receptor genes in the vomeronasal organ appear unaffe cted. Female Sp4(null) mice have a smaller thymus, spleen and uterus. In ad dition, they exhibit a pronounced delay in sexual maturation. Conclusions: The phenotype of the Sp4(null) mice differs significantly from those described for Sp1(-/-) and Sp3(-/-) mice. Thus, the structural simil arities, the common recognition motif and the overlapping expression patter n of these three transcription factors do not reflect similar physiological functions.