M. Bergwerff et al., Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus, VIRCHOWS AR, 436(1), 2000, pp. 12-19
Citations number
30
Categorie Soggetti
Medical Research Diagnosis & Treatment
Journal title
VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY
Prx1 (MHox) and Prx2 (S8) are non-clustered homeobox genes that are express
ed in a complex, mostly mesenchyme-specific pattern throughout embryogenesi
s. The expression pattern and gene-targeted mice previously revealed a majo
r role for Prx1 in skeletogenesis. In addition, specific and high expressio
n of both Prx genes was reported in the developing cardiovascular system, p
redominantly in prospective connective tissues of the heart and in the grea
t arteries and veins. We examined embryos of previously generated gene-targ
eted mice. Prx2-/- mutants were viable and did not show cardiovascular malf
ormations. Intracardiac morphology of Prx1-/- and Prx1/Prx2-combined null m
utants also appeared normal throughout development. However, the Prx-1-/- a
nd Prx1/Prx2 double-null mutants showed a vascular abnormality with an abno
rmal positioning and awkward curvature of the aortic arch in addition to a
misdirected and elongated ductus arteriosus, and in two of seven combined m
utants, an anomalous retro-oesophageal right subclavian artery. Generally,
all great arteries appeared to run somewhat tortuously through the surround
ing mesenchyme. The vascular histology and vessel wall thickness were norma
l in all mutants. Prx1-/- ann Prx double-gene-targeted mice revealed simila
r spectra of vascular anomalies, but double mutants appeared to be more ser
iously affected. The current findings suggest that other genes may compensa
te for the loss of Prx in the heart, but, in contrast, our data support a r
ole for Prx in the development of vascular and perivascular matrix.