ColVa1 and ColXIa1 are required for myocardial morphogenesis and heart valve development. Dev Dyn 2006 Dec;235(12):3295-305
Date
10/10/2006Pubmed ID
17029294DOI
10.1002/dvdy.20980Scopus ID
2-s2.0-33845362872 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
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.
Author List
Lincoln J, Florer JB, Deutsch GH, Wenstrup RJ, Yutzey KEAuthor
Joy Lincoln PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
Collagen Type I
Collagen Type III
Collagen Type IX
Collagen Type V
DNA Primers
Disease Models, Animal
Ehlers-Danlos Syndrome
Exostoses, Multiple Hereditary
Female
Fetal Heart
Gene Expression Regulation, Developmental
Heart Valves
Humans
In Situ Hybridization
Male
Mice
Mice, Knockout
Mice, Mutant Strains
Pregnancy
