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Submitted on June 9, 2003
Accepted on October 3, 2003
1 Department of Human Genetics and Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112-5331 USA
* To whom correspondence should be addressed. E-mail: mario.capecchi{at}genetics.utah.edu.
Increasing evidence indicates that the Hoxa11 gene plays a critical role in the proper development of the uterus. In this report, we describe potential altered cellular processes in the developing uterus of Hoxa11 mutants. Histologic analysis demonstrates normal uterine morphology in Hoxa11 mutants as compared with controls at the newborn stage and day 7 after birth. Stromal tissue was moderately reduced in the Hoxa11 mutant uterus by day 14 after birth and was absent by day 21 after birth. There is decreased cellular proliferation in the Hoxa11 mutant uterus both at 7 and 14 days after birth. TUNEL analysis demonstrates that apoptosis was markedly increased in the Hoxa11 mutant uterus at day 14 after birth. p27 is decreased in the Hoxa11 mutant as evidenced by real-time PCR. EGFR expression is dramatically decreased as evidenced by both real-time PCR and immunohistochemistry results. These findings suggest that Hoxa11 is required for proper cellular proliferation and apoptotic responses in the developing neonatal uterus and that the regulation of EGFR is critical to these processes.
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