Simultaneous deletion of floxed genes mediated by CaMKIIa-Cre in the brain and in male germ cells: application to conditional and conventional disruption of Goa

• Published in: Experimental & molecular medicine pp. 1 - 8
• Main Authors: 최찬일, 윤상필, 최정미, 김성수, 이영돈, Lutz Birnbaumer, 서해영
• Format: Journal Article
• Language: English
• Published: 생화학분자생물학회 01-05-2014
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

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 (CaMKIIa) promoter limits expression to specific regions of the forebrainand thus has been utilized for the brain-specific inactivation of the genes. Here, we show that CaMKIIa-Cre can be utilized forsimultaneous inactivation of genes in the adult brain and in male germ cells. Double transgenic Rosa26þ/stop-lacZ::CaMKIIa-Creþ/Cre mice generated by crossing CaMKIIa-Creþ/Cre mice with floxed ROSA26 lacZ reporter (Rosa26þ/stop-lacZ) miceexhibited lacZ expression in the brain and testis. When these mice were mated to wild-type females, about 27% ofthe offspring were whole body blue by X-gal staining without inheriting the Cre transgene. These results indicate thatrecombination can occur in the germ cells of male Rosa26þ/stop-lacZ::CaMKIIa-Creþ/Cre mice. Similarly, when double transgenicGnaoþ/f::CaMKIIa-Creþ/Cre mice carrying a floxed Go-alpha gene (Gnaof/f) were backcrossed to wild-type females, approximately22% of the offspring carried the disrupted allele (GnaoD) without inheriting the Cre transgene. The GnaoD/D mice closelyresembled conventional Go-alpha knockout mice (Gnao/) with respect to impairment of their behavior. Thus, we concludethat CaMKIIa-Cre mice afford recombination for both tissue- and time-controlled inactivation of floxed target genes in the brainand for their permanent disruption. This work also emphasizes that extra caution should be exercised in utilizing CaMKIIa-Cremice as breeding pairs. KCI Citation Count: 11