MALFORMATIONS OF THE HEART, KIDNEY, PALATE, AND SKELETON IN ALPHA-MHC-HOXB-7 TRANSGENIC MICE

被引:20
作者
ARGAO, EA [1 ]
KERN, MJ [1 ]
BRANFORD, WW [1 ]
SCOTT, WJ [1 ]
POTTER, SS [1 ]
机构
[1] CHILDRENS HOSP RES FDN, DIV BASIC SCI RES, CINCINNATI, OH 45229 USA
关键词
ALPHA-MYOSIN HEAVY CHAIN; ECTOPIC EXPRESSION; HOMEOBOX GENE; KIDNEY DEFECT; TRANSGENIC MOUSE; VENTRICULAR SEPTAL DEFECT;
D O I
10.1016/0925-4773(95)98114-P
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
To begin to define the genetic network involved in cardiogenesis, we generated mice bearing the alpha-myosin heavy chain (MHC)Hoxb-7 transgene. We hypothesized that using the cardiac-specific alpha-MHC promoter, we can direct ectopic expression of Hoxb-7 in the heart and perturb its normal development. Both whole mount in situ hybridization and northern analyses showed that this alpha-MHC promoter resulted in transgene expression in the developing heart. Severe ventricular septal defects (VSD) were found in several mutant mice. Interestingly, transgenic mice were observed to have other malformations as well, including cleft palate, renal anomalies, and skeletal abnormalities in the craniocervical and costosternal regions. The kidney defect consisted of double ureter and pelvis. In summary, we have shown that a dominant gain-of-function mutation of Hoxb-7 using the murine alpha-MHC promoter results in perturbation of the genetic circuitry underlying multiple developmental processes, including cardiogenesis. Misexpression of Hoxb-7 during heart development may be involved in the pathogenesis of VSD.
引用
收藏
页码:291 / 303
页数:13
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