title: Reciprocal knock-in mice to investigate the functional redundancy of lamin B1 and lamin B2.
abstract: Lamins B1 and B2 (B-type lamins) have very similar sequences and are expressed ubiquitously. In addition, both Lmnb1- and Lmnb2-deficient mice die soon after birth with neuronal layering abnormalities in the cerebral cortex, a consequence of defective neuronal migration. The similarities in amino acid sequences, expression patterns, and knockout phenotypes raise the question of whether the two proteins have redundant functions. To investigate this topic, we generated "reciprocal knock-in mice"-mice that make lamin B2 from the Lmnb1 locus (Lmnb1(B2/B2)) and mice that make lamin B1 from the Lmnb2 locus (Lmnb2(B1/B1)). Lmnb1(B2/B2) mice produced increased amounts of lamin B2 but no lamin B1; they died soon after birth with neuronal layering abnormalities in the cerebral cortex. However, the defects in Lmnb1(B2/B2) mice were less severe than those in Lmnb1-knockout mice, indicating that increased amounts of lamin B2 partially ameliorate the abnormalities associated with lamin B1 deficiency. Similarly, increased amounts of lamin B1 in Lmnb2(B1/B1) mice did not prevent the neurodevelopmental defects elicited by lamin B2 deficiency. We conclude that lamins B1 and B2 have unique roles in the developing brain and that increased production of one B-type lamin does not fully complement loss of the other.
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: John M
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Angelica
authors.initials: A
authors.lastname: Tatar
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Chika
authors.initials: C
authors.lastname: Nobumori
authors.affiliation: Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Hea-Jin
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, CA 94609.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoshinaga
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Catherine
authors.initials: C
authors.lastname: Coffinier
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, CA 94609.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: de Jong
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 sgyoung@mednet.ucla.edu lfong@mednet.ucla.edu.
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095 sgyoung@mednet.ucla.edu lfong@mednet.ucla.edu.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000196:embryology; D055879:Gene Knock-In Techniques; D034921:Lamin Type B / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009436:Neural Tube Defects / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics*; D034881:Nuclear Lamina / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D034921:Lamin Type B