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Generation and characterization of a conditional deletion allele for Lmna in mice.
Biochem Biophys Res Commun 2013; 440(1):8-13BB

Abstract

Extensive efforts have been devoted to study A-type lamins because mutations in their gene, LMNA in humans, are associated with a number of diseases. The mouse germline mutations in the A-type lamins (encoded by Lmna) exhibit postnatal lethality at either 4-8 postnatal (P) weeks or P16-18 days, depending on the deletion alleles. These mice exhibit defects in several tissues including hearts and skeletal muscles. Despite numerous studies, how the germline mutation of Lmna, which is expressed in many postnatal tissues, affects only selected tissues remains poorly understood. Addressing the tissue specific functions of Lmna requires the generation and careful characterization of conditional Lmna null alleles. Here we report the creation of a conditional Lmna knockout allele in mice by introducing loxP sites flanking the second exon of Lmna. The Lmna(flox/flox) mice are phenotypically normal and fertile. We show that Lmna homozygous mutants (Lmna(Δ/Δ)) generated by germline Cre expression display postnatal lethality at P16-18 days with defects similar to a recently reported germline Lmna knockout mouse that exhibits the earliest lethality compared to other germline knockout alleles. This conditional knockout mouse strain should serve as an important genetic tool to study the tissue specific roles of Lmna, which would contribute toward the understanding of various human diseases associated with A-type lamins.

Authors+Show Affiliations

Department of Embryology, Carnegie Institution for Science, 3520 San Martin Dr., Baltimore, MD 21218, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23998933

Citation

Kim, Youngjo, and Yixian Zheng. "Generation and Characterization of a Conditional Deletion Allele for Lmna in Mice." Biochemical and Biophysical Research Communications, vol. 440, no. 1, 2013, pp. 8-13.
Kim Y, Zheng Y. Generation and characterization of a conditional deletion allele for Lmna in mice. Biochem Biophys Res Commun. 2013;440(1):8-13.
Kim, Y., & Zheng, Y. (2013). Generation and characterization of a conditional deletion allele for Lmna in mice. Biochemical and Biophysical Research Communications, 440(1), pp. 8-13. doi:10.1016/j.bbrc.2013.08.082.
Kim Y, Zheng Y. Generation and Characterization of a Conditional Deletion Allele for Lmna in Mice. Biochem Biophys Res Commun. 2013 Oct 11;440(1):8-13. PubMed PMID: 23998933.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Generation and characterization of a conditional deletion allele for Lmna in mice. AU - Kim,Youngjo, AU - Zheng,Yixian, Y1 - 2013/08/30/ PY - 2013/08/22/received PY - 2013/08/24/accepted PY - 2013/9/4/entrez PY - 2013/9/4/pubmed PY - 2013/12/16/medline KW - Conditional knockout KW - Cre-loxP KW - Gene targeting KW - Laminopathies KW - Lamins KW - Lmna SP - 8 EP - 13 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 440 IS - 1 N2 - Extensive efforts have been devoted to study A-type lamins because mutations in their gene, LMNA in humans, are associated with a number of diseases. The mouse germline mutations in the A-type lamins (encoded by Lmna) exhibit postnatal lethality at either 4-8 postnatal (P) weeks or P16-18 days, depending on the deletion alleles. These mice exhibit defects in several tissues including hearts and skeletal muscles. Despite numerous studies, how the germline mutation of Lmna, which is expressed in many postnatal tissues, affects only selected tissues remains poorly understood. Addressing the tissue specific functions of Lmna requires the generation and careful characterization of conditional Lmna null alleles. Here we report the creation of a conditional Lmna knockout allele in mice by introducing loxP sites flanking the second exon of Lmna. The Lmna(flox/flox) mice are phenotypically normal and fertile. We show that Lmna homozygous mutants (Lmna(Δ/Δ)) generated by germline Cre expression display postnatal lethality at P16-18 days with defects similar to a recently reported germline Lmna knockout mouse that exhibits the earliest lethality compared to other germline knockout alleles. This conditional knockout mouse strain should serve as an important genetic tool to study the tissue specific roles of Lmna, which would contribute toward the understanding of various human diseases associated with A-type lamins. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/23998933/Generation_and_characterization_of_a_conditional_deletion_allele_for_Lmna_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(13)01429-0 DB - PRIME DP - Unbound Medicine ER -