469 Genotype-Phenotype Correlations in a Mouse Model of Ulnar-Mammary Syndrome

Abstract

In order to understand the molecular and cellular mechanisms whereby mutations in TBX3 cause the complex congenital malformations seen in humans with Ulnar-mammary syndrome, we generated a series of mutant alleles using gene targeting in mice. Since it has previously been shown that Tbx3 null mouse mutants die in mid-gestation, we generated both conditional and hypomorphic alleles to examine the effects of altered gene dosage globally, and in a tissue specific manner using Cre/loxP methodology. We used RT-PCR to determine relative levels of Tbx3 mRNA and were able to correlate gene expression with genotype and with multiple phenotypes, including cardiovascular dysfunction as assessed by in utero echocardiography, limb malformations, and embryonic lethality.