ColVa1 and ColXIa1 are required for myocardial morphogenesis and heart valve development.

Genetic mutations in minor fibrillar collagen types Va1 (ColVa1) and XIa1 (ColXI) have been identified in connective tissue disorders including Ehlers-Danlos syndrome and chondrodysplasias. ColVa1+/- and ColXIa1-/- mutant mice recapitulate these human disorders and show aberrations in collagen fiber organization in connective tissue of the skin, cornea, cartilage, and tendon. In the heart, fibrous networks of collagen fibers form throughout the ventricular myocardium and heart valves, and alterations in collagen fiber homeostasis are apparent in many forms of cardiac disease associated with myocardial dysfunction and valvular insufficiency. There is increasing evidence for cardiac dysfunction in connective tissue disorders, but the mechanisms have not been addressed. ColVa1+/- and ColXIa1-/- mutant mice were used to identify roles for ColVa1 and ColXIa1 in ventricular myocardial morphogenesis and heart valve development. These affected cardiac structures show a compensatory increase in type I collagen deposition, similar to that previously described in valvular and cardiomyopathic disease. Morphological cardiac defects associated with changes in collagen fiber homeostasis identified in ColVa1+/- and ColXIa1-/- mice provide an insight into previously unappreciated forms of cardiac dysfunction associated with connective tissue disorders.