Cardiac dysfunction in transgenic mouse fetuses overexpressing shortened type XIII collagen.
Overexpression of type XIII collagen molecules with an 83-amino-acid residue in-frame deletion of part of the ectodomain leads to fetal lethality in Col13a1COL2del transgenic mice. We characterize here the functional disturbances in the cardiovascular system of mouse fetuses overexpressing mutant type XIII collagen. Doppler ultrasonography was performed at 12.5 days of gestation on 33 fetuses resulting from heterozygous matings of seven female mice and on 16 fetuses from two matings between heterozygous and wild-type mice. Nine fetuses had atrioventricular valve regurgitation (AVVR), and all of them were transgene-positive. The fetuses with AVVR had a lower outflow mean velocity (Vmean; P<0.005) and a greater proportion of isovolumetric relaxation time (IRT%) in the cardiac cycle (P<0.0001) than those without AVVR, and their ductus venosus pulsatility indices for veins (DV PIV) and the umbilical artery pulsatility indices were increased. A positive correlation was found between IRT% and DV PIV, and a negative correlation was seen between outflow V(mean) and DV PIV. Morphological analysis of the heart revealed no differences between the two groups of fetuses, but histological analysis showed the trabeculation of the ventricles to be reduced and the myocardium to be thinner in the fetuses with AVVR. Based on in situ hybridization, type XIII collagen mRNAs were normal constituents of these structures. Moreover, a positive correlation was found between outflow Vmean and myocardial thickness. IRT% and DV PIV correlated negatively with myocardial thickness. Thus, overexpression of mutant type XIII collagen results in mid-gestation cardiac dysfunction in mouse fetuses, and these disturbances in cardiac function may lead to death in utero.
Tahkola
Jenni
J
Oulu Center to Cell-Matrix Research, Biocenter Oulu, Department of Medical Biochemistry and Molecular Biology, University of Oulu, P. O. Box 5000, 90014, Oulu, Finland.
Räsänen
Juha
J
Sund
Malin
M
Mäkikallio
Kaarin
K
Autio-Harmainen
Helena
H
Pihlajaniemi
Taina
T
D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D024181:Collagen Type XIII / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005318:Fetal Heart / Q000000981:diagnostic imaging / Q000196:embryology / Q000503:physiopathology*; D005333:Fetus / Q000098:blood supply; D005865:Gestational Age; D006579:Heterozygote; D006720:Homozygote; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D011247:Pregnancy; D019076:Transgenes; D018608:Ultrasonography, Doppler / Q000379:methods; D016216:Ultrasonography, Prenatal / Q000379:methods; D014469:Umbilical Arteries / Q000000981:diagnostic imaging; D014471:Umbilical Veins / Q000000981:diagnostic imaging
D024181:Collagen Type XIII