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Publication : Malformations of the heart, kidney, palate, and skeleton in alpha-MHC-Hoxb-7 transgenic mice.

First Author  Argao EA Year  1995
Journal  Mech Dev Volume  52
Issue  2-3 Pages  291-303
PubMed ID  8541217 Mgi Jnum  J:28713
Mgi Id  MGI:76257 Doi  10.1016/0925-4773(95)98114-p
Citation  Argao EA, et al. (1995) Malformations of the heart, kidney, palate, and skeleton in alpha-MHC-Hoxb-7 transgenic mice. Mech Dev 52(2-3):291-303
abstractText  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.
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