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Generation of mice with a conditional Lbh null allele
Linsey E Lindley1, Karoline J Briegel
1Department 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.
Genesis (New York, N.Y. : 2000)
|March 16, 2013
Summary
Researchers created conditional knockout mice to study Limb bud and heart (LBH), a protein involved in WNT signaling. LBH loss did not affect embryonic development but impaired mammary gland growth, revealing its specific postnatal roles.
Area of Science:
- Developmental Biology
- Molecular Genetics
- Cancer Biology
Background:
- Limb bud and heart (LBH) is a transcription cofactor crucial for WNT signaling, vital for embryogenesis and tissue homeostasis.
- Gain-of-function mutations in LBH are linked to congenital diseases and cancer, but its normal function is unknown due to lack of loss-of-function models.
Purpose of the Study:
- To generate a conditional knockout mouse model for Lbh to investigate its physiological roles.
- To elucidate the tissue-specific functions of LBH in postnatal development and disease.
Main Methods:
- Generated mice with a conditional null allele of Lbh by flanking exon 2 with loxP sites (Lbh(flox)).
- Utilized FLPe-mediated recombination to remove the Neo cassette, creating functional Lbh(loxP) alleles.
- Crossed Lbh(loxP) mice with a Rosa26-Cre line to achieve ubiquitous deletion of exon 2, generating Lbh null mice (Lbh(Δ)(2)).
Main Results:
- Conditional Lbh alleles were fully functional, with homozygous mice being viable and fertile.
- Lbh null mice (Lbh(Δ)(2)) showed normal embryonic development and postnatal growth.
- Mammary gland development was perturbed in Lbh null mice, indicating a specific role in this postnatal process.
Conclusions:
- The conditional Lbh allele is a valuable tool for studying LBH function.
- LBH plays a critical, previously unknown role in postnatal mammary gland development.
- This model will aid in uncovering tissue-specific functions of LBH in development and disease.
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