Generation of mice with a conditional Lbh null allele

Limb bud and heart (LBH) is a developmentally expressed, tissue‐specific transcription cofactor in vertebrates that acts in the WNT signaling pathway, a genetic program critical for embryogenesis and adult tissue homeostasis. Aberrant gain‐of‐function of LBH is implicated in both human congenital disease and cancer. The normal physiological function of LBH has remained elusive owing to a lack of genetic loss‐of‐function models. Here, we have generated mice with a conditional null allele of Lbh by flanking exon 2 with loxP sites (Lbh^flox). Homozygous Lbh^flox and Lbh^loxP mice, in which the Neo cassette was removed through FLPe‐mediated recombination, were viable and fertile, indicating that these conditional Lbh alleles are fully functional. Lbh^loxP mice were then crossed with a Rosa26‐Cre line, resulting in ubiquitous deletion of exon 2 and abolishment of LBH protein expression. Mice homozygous for the Lbh null allele (Lbh^Δ2) displayed normal embryonic development and postnatal growth with morphologies indistinguishable from wild‐type littermates. However, mammary gland development, which occurs primarily after birth, was perturbed. Thus, the conditional Lbh allele will be a valuable tool to uncover the currently unknown tissue‐specific roles of LBH in postnatal development and disease. genesis 51:491–497. © 2013 Wiley Periodicals, Inc.