| Title: | Simultaneous deletion of floxed genes mediated by CaMKIIalpha-Cre in the brain and in male germ cells: application to conditional and conventional disruption of Goalpha |
| Author(s): | Choi CI; Yoon SP; Choi JM; Kim SS; Lee YD; Birnbaumer L; Suh-Kim H; |
| Address: | "1] Departments of Anatomy, Ajou University, School of Medicine, Suwon, South Korea [2] Neuroscience Graduate Program, Ajou University, School of Medicine, Suwon, South Korea [3] BK21-Division of Cell Transformation and Restoration, Ajou University, School of Medicine, Suwon, South Korea. 1] Departments of Anatomy, Ajou University, School of Medicine, Suwon, South Korea [2] Center for Cell Death Regulating Biodrug, Ajou University, School of Medicine, Suwon, South Korea. 1] Departments of Anatomy, Ajou University, School of Medicine, Suwon, South Korea [2] Center for Cell Death Regulating Biodrug, Ajou University, School of Medicine, Suwon, South Korea [3] Department of Molecular Science and Technology, Ajou University, Suwon, South Korea. National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA" |
| ISSN/ISBN: | 2092-6413 (Electronic) 1226-3613 (Print) 1226-3613 (Linking) |
| Abstract: | "The Cre/LoxP system is a well-established approach to spatially and temporally control genetic inactivation. The calcium/calmodulin-dependent protein kinase II alpha subunit (CaMKIIalpha) promoter limits expression to specific regions of the forebrain and thus has been utilized for the brain-specific inactivation of the genes. Here, we show that CaMKIIalpha-Cre can be utilized for simultaneous inactivation of genes in the adult brain and in male germ cells. Double transgenic Rosa26(+/stop-lacZ)::CaMKIIalpha-Cre(+/Cre) mice generated by crossing CaMKIIalpha-Cre(+/Cre) mice with floxed ROSA26 lacZ reporter (Rosa26(+/stop-lacZ)) mice exhibited lacZ expression in the brain and testis. When these mice were mated to wild-type females, about 27% of the offspring were whole body blue by X-gal staining without inheriting the Cre transgene. These results indicate that recombination can occur in the germ cells of male Rosa26(+/stop-lacZ)::CaMKIIalpha-Cre(+/Cre) mice. Similarly, when double transgenic Gnao(+/f)::CaMKIIalpha-Cre(+/Cre) mice carrying a floxed Go-alpha gene (Gnao(f/f)) were backcrossed to wild-type females, approximately 22% of the offspring carried the disrupted allele (Gnao(Delta)) without inheriting the Cre transgene. The Gnao(Delta/Delta) mice closely resembled conventional Go-alpha knockout mice (Gnao(-/-)) with respect to impairment of their behavior. Thus, we conclude that CaMKIIalpha-Cre mice afford recombination for both tissue- and time-controlled inactivation of floxed target genes in the brain and for their permanent disruption. This work also emphasizes that extra caution should be exercised in utilizing CaMKIIalpha-Cre mice as breeding pairs" |
| Keywords: | "Animals Brain/*metabolism Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics Female GTP-Binding Protein alpha Subunits, Gi-Go/*genetics *Gene Deletion Gene Knockout Techniques/*methods Male Mice RNA, Untranslated/genetics Recombination, Genetic S;Neuroscience;" |
| Notes: | "MedlineChoi, Chan-Il Yoon, Sang-Phil Choi, Jung-Mi Kim, Sung-Soo Lee, Young-Don Birnbaumer, Lutz Suh-Kim, Haeyoung eng Z01 ES101643/Intramural NIH HHS/ Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't 2014/05/03 Exp Mol Med. 2014 May 2; 46(5):e93. doi: 10.1038/emm.2014.14" |
