Genetic evidence suggests that the distal tip of human chromosome 21, partially or wholly duplicated in Down Syndrome (DS), contributes to the development of congenital heart defects. COL6A2 (collagen, type VI, alpha 2) and DSCAM (DS cell adhesion molecule), both located in this critical genomic region, have now been found to cooperatively generate cardiac deficiencies.

These alpha-MHC-COL6A2 transgenic mice express human COL6A2 cDNA from the mouse Myh6 promoter (myosin, heavy polypeptide 6, cardiac muscle, alpha; &alpha; MHC), which is active in myocardial cells both during early development and in the adult.

On its own, this transgene does not affect viability and has little or no effect on heart physiology of morphology. However, when alpha-MHC-COL6A2 mice are crossed to alpha-MHC-DSCAM mice (Stock No. <a href="https://www.jax.org/strain/031927">031927</a>) expressing comparable levels of DSCAM, double transgenic adult mice are recovered at only 58% of the expected frequency. Double transgenic adult mice hearts exhibit an increased thickness of the left ventricle (LV) wall and interventricular septum (IVS) relative to control wild-type hearts, and 53% of the double transgenic mice exhibit functional atrial septal defects (ASD). In the most extreme double transgenic hearts, digital reconstruction of the heart chambers reveals that the walls of the left ventricle are enlarged to the point of nearly occluding the lumen; the interventricular septum and right ventricular walls are also thickened. Though the left ventricular myopathy is not typical of Down Syndrome congenital heart disease, the phenotype of this gene-cooperative model is highly penetrant and may speak to the etiology of various forms of cardiac hypertrophy, such as those resulting from increased load.

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Alpha-MHC-COL6A2 transgenic mice express human COL6A2 cDNA from the mouse cardiac-specific Myh6 promoter. Over-expression of human COL6A2 and mouse Dscam has been found to cooperatively generate congenital heart defects. This alpha-MHC-COL6A2 strain may help characterize the congenital heart defects associated with Down Syndrome; especially when used in conjunction with alpha-MHC-DSCAM transgenic mice (Stock No. <a href="https://www.jax.org/strain/031927">031927</a>).

Typically mice are recovered in 12-16 weeks. Contact Customer Service to place an order or for more information.

<a target="_blank" href="https://www.jax.org/jax-mice-and-services/customer-support" rel="noreferrer">Contact Customer Service</a> for more information.