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Molecular and Cellular Biology, November 2001, p. 7481-7494, Vol. 21, No. 21
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.21.7481-7494.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Isolation of a Murine Homologue of the Drosophila neuralized Gene, a Gene Required for Axonemal Integrity in Spermatozoa and Terminal Maturation of the Mammary Gland

Benedikt Vollrath,1,dagger Jeffrey Pudney,2 Sylvia Asa,3 Philip Leder,1,* and Kevin Fitzgerald1,Dagger

Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School,1 and Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School,2 Boston, Massachusetts 02115, and Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X53

Received 5 June 2001/Returned for modification 11 July 2001/Accepted 31 July 2001

The Drosophila neuralized gene shows genetic interactions with Notch, Enhancer of split, and other neurogenic genes and is thought to be involved in cell fate specification in the central nervous system and the mesoderm. In addition, a human homologue of the Drosophila neuralized gene has been described as a potential tumor suppressor gene in malignant astrocytomas. We have isolated a murine homologue of the Drosophila and human Neuralized genes and, in an effort to understand its physiological function, derived mice with a targeted deletion of this gene. Surprisingly, mice homozygous for the introduced mutation do not show aberrant cell fate specifications in the central nervous system or in the developing mesoderm. This is in contrast to mice with targeted deletions in other vertebrate homologues of neurogenic genes such as Notch, Delta, and Cbf-1. Male Neuralized null mice, however, are sterile due to a defect in axoneme organization in the spermatozoa that leads to highly compromised tail movement and sperm immotility. In addition, female Neuralized null animals are defective in the final stages of mammary gland maturation during pregnancy.

* Corresponding author. Mailing address: Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 432-7667. Fax: (617) 432-7944. E-mail: leder{at}rascal.med.harvard.edu.

dagger Present address: Merck Research Laboratories, West Point, PA 19486.

Dagger Present address: Bristol Myers Squibb, Pennington, NJ 08530.

Molecular and Cellular Biology, November 2001, p. 7481-7494, Vol. 21, No. 21
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.21.7481-7494.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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