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Molecular and Cellular Biology, November 2001, p. 7243-7255, Vol. 21, No. 21
Departments of Experimental Radiation
Oncology1 and Molecular
Genetics,2 University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Department of
Physiology, Southern Illinois University School of Medicine,
Carbondale, Illinois 629013
Received 24 April 2001/Returned for modification 5 July
2001/Accepted 31 July 2001
During mammalian spermiogenesis, major restructuring of chromatin
takes place. In the mouse, the histones are replaced by the transition
proteins, TP1 and TP2, which are in turn replaced by the protamines, P1
and P2. To investigate the role of TP2, we generated mice with a
targeted deletion of its gene, Tnp2. Spermatogenesis in
Tnp2 null mice was almost normal, with testis weights and
epididymal sperm counts being unaffected. The only abnormality in
testicular histology was a slight increase of sperm retention in stage
IX to XI tubules. Epididymal sperm from Tnp2-null mice
showed an increase in abnormal tail, but not head, morphology. The mice
were fertile but produced small litters. In step 12 to 16 spermatid
nuclei from Tnp2-null mice, there was normal displacement of histones, a compensatory translationally regulated increase in TP1
levels, and elevated levels of precursor and partially processed forms
of P2. Electron microscopy revealed abnormal focal condensations of
chromatin in step 11 to 13 spermatids and progressive chromatin
condensation in later spermatids, but condensation was still incomplete
in epididymal sperm. Compared to that of the wild type, the sperm
chromatin of these mutants was more accessible to intercalating dyes
and more susceptible to acid denaturation, which is believed to
indicate DNA strand breaks. We conclude that TP2 is not a critical
factor for shaping of the sperm nucleus, histone displacement,
initiation of chromatin condensation, binding of protamines to DNA, or
fertility but that it is necessary for maintaining the normal
processing of P2 and, consequently, the completion of chromatin condensation.
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.21.7243-7255.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Targeted Disruption of the Transition Protein 2 Gene Affects Sperm Chromatin Structure and Reduces Fertility in
Mice





*
Corresponding author. Mailing address: Department of
Experimental Radiation Oncology, Box 66, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Phone: (713) 794-4858. Fax:
(713) 794-5369. E-mail: mzhao{at}mdanderson.org.
This paper is dedicated to the memory of Lonnie Russell and his
many contributions to our understanding of spermatogenesis.
Present address: Department of Molecular and Human Genetics,
Baylor College of Medicine, Houston, TX 77030.
§
Present address: Department of Pediatrics-Cardiology, Baylor
College of Medicine, Houston, TX 77030.
Present address: Cancer Biology, Chemical Industry Institute of
Toxicology, Centers for Health Research, Research Triangle Park, NC 27709.
#
Present address: Department of Molecular and Cellular Biology,
Baylor College of Medicine, Houston, TX 77030.

Deceased 11 July 2001.
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