Cardiac dysfunction in transgenic mouse fetuses overexpressing shortened type XIII collagen

Jenni Tahkola, Juha Räsänen, Malin Sund, Kaarin Mäkikallio, Helena Autio-Harmainen, Taina Pihlajaniemi

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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 Col13a1 COL2del 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 Vmean 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 V mean 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.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalCell and tissue research
Volume333
Issue number1
DOIs
StatePublished - Jul 1 2008

Keywords

  • Atrioventricular valve regurgitation
  • Col13a1
  • Collagen
  • Heart failure
  • Mouse
  • Ultrasonics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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    Tahkola, J., Räsänen, J., Sund, M., Mäkikallio, K., Autio-Harmainen, H., & Pihlajaniemi, T. (2008). Cardiac dysfunction in transgenic mouse fetuses overexpressing shortened type XIII collagen. Cell and tissue research, 333(1), 61-69. https://doi.org/10.1007/s00441-008-0617-5