HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 70/2/371    most recent biolreprod.103.021600v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fischer, C. Articles by Rawls, A. Search for Related Content PubMed PubMed Citation Articles by Fischer, C. Articles by Rawls, A. Agricola Articles by Fischer, C. Articles by Rawls, A.

Activating Transcription Factor 4 Is Required for the Differentiation of the Lamina Propria Layer of the Vas Deferens¹

School of Life Sciences,⁴ Arizona State University, Tempe, Arizona 85287 Molecular and Cellular Biology Graduate Program,⁵ Arizona State University, Tempe, Arizona 85287 Center for Evolutionary Functional Genomics,⁶ Arizona BioDesign Institute, Arizona State University, Tempe, Arizona 85287-4501

Activating transcription factor 4 (ATF4/CREB2) is a member of the cyclic-AMP response element-binding (CREB) family. These proteins have been shown to regulate cell proliferation and differentiation in a broad number of tissues during embryo development. Here we report that male ATF4^-/- mice are subfertile, despite the fact that they produce sufficient sperm and are able to fertilize wild-type eggs in vitro. An analysis of the ejaculatory ducts revealed abnormal constrictions in the lumen of the vas deferens. The lamina propria layer of the vas deferens was significantly thicker in the ATF4^-/- mice and the cells that make up this layer were rounder and more abundant than in the ATF4^+/+ littermates. The change in the morphology of the lamina propria was associated with sexual maturation. A histologic analysis of the lamina propria revealed a reduction in the production of elastic fibers and interstitial cells of Cajal, as judged by the expression of neuron-specific enolase. These observations predict that ATF4 is required for the normal differentiation of the lamina propria layer of the vas deferens at sexual maturation. The morphology of the ATF4^-/- lamina propria and the constriction of the lumen are consistent with an obstruction in the vas deferens contributing to the subfertility of the ATF4^-/- males.

¹ This research was supported by National Science Foundation grant IBN-0131726.

² Correspondence: Alan Rawls, School of Life Sciences, Life Sciences C Bldg., Rm. 544, Arizona State University, Tempe, AZ 85287-4501. FAX: 480 965 2519; jrawls{at}imap4.asu.edu

³ Current address: Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114

This article has been cited by other articles:

				H. Fung, P. Liu, and B. Demple ATF4-Dependent Oxidative Induction of the DNA Repair Enzyme Ape1 Counteracts Arsenite Cytotoxicity and Suppresses Arsenite-Mediated Mutagenesis Mol. Cell. Biol., December 15, 2007; 27(24): 8834 - 8847. [Abstract] [Full Text] [PDF]

				X. Yang and G. Karsenty ATF4, the Osteoblast Accumulation of Which Is Determined Post-translationally, Can Induce Osteoblast-specific Gene Expression in Non-osteoblastic Cells J. Biol. Chem., November 5, 2004; 279(45): 47109 - 47114. [Abstract] [Full Text] [PDF]