| Title: | Disruption of CCTbeta2 expression leads to gonadal dysfunction |
| Author(s): | Jackowski S; Rehg JE; Zhang YM; Wang J; Miller K; Jackson P; Karim MA; |
| Address: | "Protein Science Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA. suzanne.jackowski@stjude.org" |
| DOI: | 10.1128/MCB.24.11.4720-4733.2004 |
| ISSN/ISBN: | 0270-7306 (Print) 1098-5549 (Electronic) 0270-7306 (Linking) |
| Abstract: | "There are two mammalian genes that encode isoforms of CTP:phosphocholine cytidylyltransferase (CCT), a key rate-controlling step in membrane phospholipid biogenesis. Quantitative determination of the CCT transcripts reveals that CCTalpha is ubiquitously expressed and is found at the highest levels in the testis and lung, with lower levels in the liver and ovary. CCTbeta2 is a very minor isoform in most tissues but is significantly expressed in the brain, lung, and gonads. CCTbeta3 is the third isoform recently discovered in mice and is expressed in the same tissues as CCTbeta2, with its highest level in testes. We investigated the role(s) of CCTbeta2 by generating knockout mice. The brains and lungs of mice lacking CCTbeta2 expression did not exhibit any overt defects. On the other hand, a large percentage of the CCTbeta2(-/-) females were sterile and their ovaries exhibited defective ovarian follicle development. The proportion of female CCTbeta2(-/-) mice with defective ovaries increased as the animals aged. The rare litters born from CCTbeta2(-/-) x CCTbeta2(-/0) matings had the normal number of pups. The abnormal ovarian histopathology was characterized by disorganization of the tissue in young adult mice and absence of follicles and ova in older mice, along with interstitial stromal cell hyperplasia which culminated in the emergence of tubulostromal ovarian tumors by 16 months of age. Grossly defective CCTbeta2(-/-) ovaries were associated with high follicle-stimulating (FSH) and luteinizing (LH) hormone levels. Male CCTbeta2(-/0) mice exhibited progressive multifocal testicular degeneration and reduced fertility but had normal FSH and LH levels. Thus, the most notable phenotype of CCTbeta2 knockout mice was gonad degeneration and reproductive deficiency. The results indicate that although CCTbeta2 is expressed at very low levels compared to the alpha-isoform, loss of CCTbeta2 expression causes a breakdown in the gonadal response to hormonal stimulation" |
| Keywords: | "Animals Choline-Phosphate Cytidylyltransferase/genetics/*metabolism Female Genitalia/embryology/*physiology Immunoblotting Male Mice Mice, Knockout Ovary/pathology RNA, Messenger/metabolism Reproduction/physiology Testis/pathology;" |
| Notes: | "MedlineJackowski, Suzanne Rehg, Jerold E Zhang, Yong-Mei Wang, Jina Miller, Karen Jackson, Pam Karim, Mohammad A eng HD28934/HD/NICHD NIH HHS/ R01 GM045737/GM/NIGMS NIH HHS/ U54 HD028934/HD/NICHD NIH HHS/ P30 CA021765/CA/NCI NIH HHS/ CA 21765/CA/NCI NIH HHS/ GM45737/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2004/05/15 Mol Cell Biol. 2004 Jun; 24(11):4720-33. doi: 10.1128/MCB.24.11.4720-4733.2004" |
