Premium
Patterning of coronary arteries in wildtype and connexin43 knockout mice
Author(s) -
Clauss Sarah B.,
Walker Diana L.,
Kirby Margaret L.,
Schimel Dan,
Lo Cecilia W.
Publication year - 2006
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20887
Subject(s) - coronary arteries , right coronary artery , artery , wild type , biology , circumflex , anatomy , haploinsufficiency , knockout mouse , aorta , cardiology , medicine , coronary angiography , phenotype , genetics , gene , myocardial infarction , mutant
Abnormal patterning of coronary arteries (CAs) is a clinically significant problem, and as yet, few animal models have been systematically investigated for coronary patterning defects. Here we characterized coronary artery (CA) insertion and branching patterns of the proximal coronary stems in the hearts of wildtype and heterozygous connexin43 knockout (Cx43α1 KO) mice. This study entailed the use of high‐resolution micro CT imaging for three‐dimensional coronary reconstructions. MicroCT of 17 wildtype mice showed a remarkably consistent pattern of CA deployment in the normal mouse heart. Two main CA stems are inserted from the left and right into the aorta. The right coronary artery then branches immediately into the right main and the septal‐conal branch, while the left coronary artery branches further distally into the circumflex and the anterior descending CA. This patterning of CA anatomy was confirmed by histology, and by using a vascular smooth muscle or endothelial cell specific lacZ reporter gene to delineate the CAs. A parallel analysis of 25 heterozygous Cx43α1 KO mouse hearts showed 22 had defects in patterning of the CAs. They exhibited a wide variation in CA anatomy, including abnormal origin and course of the main CA stems, multiple accessories, and dual septal‐conal branches. Overall, these studies show loss of one Cx43α1 allele (haploinsufficiency) leads to a high incidence of coronary patterning defects. These findings suggest CA patterning is sensitive to Cx43α1 gene dosage. Developmental Dynamics 235:2786–2794, 2006. Published 2006 Wiley‐Liss, Inc.