Disruption of the Hoxa3 homeobox gene results in anomalies of the carotid artery system and the arterial baroreceptors.

Homeobox gene Hoxa3 is expressed in the third pharyngeal arch and pouch and is required for development of the third arch artery in addition to the thymus, parathyroid gland and carotid body. We therefore statistically analyzed malformations of the carotid artery system in Hoxa3 homozygous mutant mice, in comparison with wild-type and heterozygous littermates. To identify the carotid artery system, red carbon ink was injected, or vascular casts were made by injection of Mercox resin and observed by scanning electron microscopy. Furthermore, innervation of the carotid sinus and baroreceptor regions in the aortic arch and right subclavian artery were studied in the Hoxa3 null mutants having an abnormal carotid artery system by immunohistochemistry with TuJ1 and protein gene product (PGP) 9.5 antibodies, which recognize nerve fibers and neurons. The common carotid artery of Hoxa3 homozygous mutants was absent or very short and therefore the internal and external carotid artery arose from a more proximal level than those of wild types. The baroreceptor innervation, however, persisted in the mutants, although vascular targets were changed. These results indicate that Hoxa3 gene is crucial for the formation of the common carotid artery and the null mutant mice are the first useful animal models to show that the third arch arteries on both sides specifically degenerate but the fourth and sixth arch arteries are normal.