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Generation of mice with a conditional Lbh null allele.
Genesis 2013; 51(7):491-7G

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+Show Affiliations

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.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23495064

Citation

Lindley, Linsey E., and Karoline J. Briegel. "Generation of Mice With a Conditional Lbh Null Allele." Genesis (New York, N.Y. : 2000), vol. 51, no. 7, 2013, pp. 491-7.
Lindley LE, Briegel KJ. Generation of mice with a conditional Lbh null allele. Genesis. 2013;51(7):491-7.
Lindley, L. E., & Briegel, K. J. (2013). Generation of mice with a conditional Lbh null allele. Genesis (New York, N.Y. : 2000), 51(7), pp. 491-7. doi:10.1002/dvg.22390.
Lindley LE, Briegel KJ. Generation of Mice With a Conditional Lbh Null Allele. Genesis. 2013;51(7):491-7. PubMed PMID: 23495064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Generation of mice with a conditional Lbh null allele. AU - Lindley,Linsey E, AU - Briegel,Karoline J, Y1 - 2013/05/03/ PY - 2013/02/07/received PY - 2013/02/28/revised PY - 2013/03/04/accepted PY - 2013/3/16/entrez PY - 2013/3/16/pubmed PY - 2014/1/24/medline KW - Cre-loxP KW - LBH KW - conditional knockout KW - mammary gland development SP - 491 EP - 7 JF - Genesis (New York, N.Y. : 2000) JO - Genesis VL - 51 IS - 7 N2 - 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. SN - 1526-968X UR - https://www.unboundmedicine.com/medline/citation/23495064/Generation_of_mice_with_a_conditional_Lbh_null_allele_ L2 - https://doi.org/10.1002/dvg.22390 DB - PRIME DP - Unbound Medicine ER -