Cardiovascular defects associated with abnormalities in midline development in the Loop-tail mouse mutant

Deborah J. Henderson, Simon Conway, Nicholas D E Greene, Dianne Gerrelli, Jennifer N. Murdoch, Robert H. Anderson, Andrew J. Copp

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Loop-tail (Lp) is a naturally occurring mouse mutant that develops severe neural tube defects. In this study, we describe complex cardiovascular defects in Lp homozygotes, which include double-outlet right ventricle, with obligatory perimembranous ventricular septal defects, and double-sided aortic arch, with associated abnormalities in the aortic arch arteries. Outflow tract and aortic arch defects are often related to abnormalities in the cardiac neural crest, but using molecular and anatomic markers, we show that neural crest migration is normal in Lp/Lp embryos. On the other hand, the heart fails to loop normally in Lp/Lp embryos, in association with incomplete axial rotation and reduced cervical flexion. As a consequence, the ventricular loop is shifted posteromedially relative to its position in wild-type embryos. This suggests that the observed cardiac alignment defects in the Lp mutant may be secondary to failure of neural tube closure and incomplete axial rotation. Double-sided aortic arch is a rare finding among mouse models. In humans, it is usually an isolated malformation, only rarely occurring in combination with other cardiac defects. We suggest that the double-sided arch arises as a primary defect in the Lp mutant, unrelated to the alignment defects, perhaps reflecting a role for the (as-yet-unknown) Lp gene in maintenance/regression of the aortic arch system.

Original languageEnglish (US)
Pages (from-to)6-12
Number of pages7
JournalCirculation Research
Volume89
Issue number1
StatePublished - Jul 6 2001
Externally publishedYes

Fingerprint

Tail
Thoracic Aorta
Embryonic Structures
Neural Crest
Double Outlet Right Ventricle
Neural Tube
Neural Tube Defects
Ventricular Heart Septal Defects
Homozygote
Arteries
Maintenance
Genes

Keywords

  • Congenital heart defects
  • Double-outlet right ventricle
  • Double-sided aortic arch
  • Midline defects
  • Mouse mutants

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Henderson, D. J., Conway, S., Greene, N. D. E., Gerrelli, D., Murdoch, J. N., Anderson, R. H., & Copp, A. J. (2001). Cardiovascular defects associated with abnormalities in midline development in the Loop-tail mouse mutant. Circulation Research, 89(1), 6-12.

Cardiovascular defects associated with abnormalities in midline development in the Loop-tail mouse mutant. / Henderson, Deborah J.; Conway, Simon; Greene, Nicholas D E; Gerrelli, Dianne; Murdoch, Jennifer N.; Anderson, Robert H.; Copp, Andrew J.

In: Circulation Research, Vol. 89, No. 1, 06.07.2001, p. 6-12.

Research output: Contribution to journalArticle

Henderson, DJ, Conway, S, Greene, NDE, Gerrelli, D, Murdoch, JN, Anderson, RH & Copp, AJ 2001, 'Cardiovascular defects associated with abnormalities in midline development in the Loop-tail mouse mutant', Circulation Research, vol. 89, no. 1, pp. 6-12.
Henderson DJ, Conway S, Greene NDE, Gerrelli D, Murdoch JN, Anderson RH et al. Cardiovascular defects associated with abnormalities in midline development in the Loop-tail mouse mutant. Circulation Research. 2001 Jul 6;89(1):6-12.
Henderson, Deborah J. ; Conway, Simon ; Greene, Nicholas D E ; Gerrelli, Dianne ; Murdoch, Jennifer N. ; Anderson, Robert H. ; Copp, Andrew J. / Cardiovascular defects associated with abnormalities in midline development in the Loop-tail mouse mutant. In: Circulation Research. 2001 ; Vol. 89, No. 1. pp. 6-12.
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