title: Generation of mice with a conditional Lbh null allele.
abstract: 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(Δ)(2)) 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Braman Family Breast Cancer Institute at the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Linsey E
authors.initials: LE
authors.lastname: Lindley
authors.forename: Karoline J
authors.initials: KJ
authors.lastname: Briegel
mesh_terms: D000483:Alleles; D000818:Animals; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D008297:Male; D008321:Mammary Glands, Animal / Q000254:growth & development*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors
chemical_list: D018797:Cell Cycle Proteins; C428223:Lbh protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: Cre-loxP; LBH; conditional knockout; mammary gland development