About Us |
PMID | 27833122 |
Gene Name | PRM2 |
Condition | Male infertility |
Association |
Associated |
Sex | Male |
Infertility type | Male infertility |
Other associated phenotypes |
Male infertility |
Re-visiting the Protamine-2 locus: deletion, but not haploinsufficiency, renders male mice infertile Schneider S, Balbach M, Jan F Jikeli, Fietz D, Nettersheim D, Jostes S, Schmidt R, Kressin M, Bergmann M, Wachten D, Steger K, Schorle H. Protamines are arginine-rich DNA-binding proteins that replace histones in elongating spermatids. This leads to hypercondensation of chromatin and ensures physiological sperm morphology, thereby protecting DNA integrity. In mice and humans, two protamines, protamine-1 (Prm1) and protamine-2 (Prm2) are expressed in a species-specific ratio. In humans, alterations of this PRM1/PRM2 ratio is associated with subfertility. By applying CRISPR/Cas9 mediated gene-editing in oocytes, we established Prm2-deficient mice. Surprisingly, heterozygous males remained fertile with sperm displaying normal head morphology and motility. In Prm2-deficient sperm, however, DNA-hypercondensation and acrosome formation was severely impaired. Further, the sperm displayed severe membrane defects resulting in immotility. Thus, lack of Prm2 leads not only to impaired histone to protamine exchange and disturbed DNA-hypercondensation, but also to severe membrane defects resulting in immotility. Interestingly, previous attempts using a regular gene-targeting approach failed to establish Prm2-deficient mice. This was due to the fact that already chimeric animals generated with Prm2(+/-) ES cells were sterile. However, the Prm2-deficient mouse lines established here clearly demonstrate that mice tolerate loss of one Prm2 allele. As such they present an ideal model for further studies on protamine function and chromatin organization in murine sperm. FAU - Schneider, Simon AU - Schneider S AD - Institute of Pathology, Department of Developmental Pathology, University of Bonn Medical School, Bonn, Germany. FAU - Balbach, Melanie AU - Balbach M AD - Minerva Max Planck Research Group - Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany. FAU - Jan F Jikeli AU - Jan F Jikeli AD - Minerva Max Planck Research Group - Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany. FAU - Fietz, Daniela AU - Fietz D AD - Institute of Veterinary-Anatomy, -Histology and -Embryology, Justus-Liebig University, Giessen, Germany. FAU - Nettersheim, Daniel AU - Nettersheim D AD - Institute of Pathology, Department of Developmental Pathology, University of Bonn Medical School, Bonn, Germany. FAU - Jostes, Sina AU - Jostes S AD - Institute of Pathology, Department of Developmental Pathology, University of Bonn Medical School, Bonn, Germany. FAU - Schmidt, Rovenna AU - Schmidt R AD - Institute of Veterinary-Anatomy, -Histology and -Embryology, Justus-Liebig University, Giessen, Germany. FAU - Kressin, Monika AU - Kressin M AD - Institute of Veterinary-Anatomy, -Histology and -Embryology, Justus-Liebig University, Giessen, Germany. FAU - Bergmann, Martin AU - Bergmann M AD - Institute of Veterinary-Anatomy, -Histology and -Embryology, Justus-Liebig University, Giessen, Germany. FAU - Wachten, Dagmar AU - Wachten D AD - Minerva Max Planck Research Group - Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany. FAU - Steger, Klaus AU - Steger K AD - Department of Urology, Pediatric Urology and Andrology, Section Molecular Andrology, Biomedical Research Center of the Justus-Liebig University, Giessen, Germany. |