title: Generation and characterization of a conditional deletion allele for Lmna in mice.
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.affiliation: Department of Embryology, Carnegie Institution for Science, 3520 San Martin Dr., Baltimore, MD 21218, USA.
authors.forename: Youngjo
authors.initials: Y
authors.lastname: Kim
authors.forename: Yixian
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: D034904:Lamin Type A; C576142:Lmna protein, mouse
keywords: Conditional knockout; Cre-loxP; Gene targeting; Laminopathies; Lamins; Lmna