title: Deficiencies in lamin B1 and lamin B2 cause neurodevelopmental defects and distinct nuclear shape abnormalities in neurons.
abstract: Neuronal migration is essential for the development of the mammalian brain. Here, we document severe defects in neuronal migration and reduced numbers of neurons in lamin B1-deficient mice. Lamin B1 deficiency resulted in striking abnormalities in the nuclear shape of cortical neurons; many neurons contained a solitary nuclear bleb and exhibited an asymmetric distribution of lamin B2. In contrast, lamin B2 deficiency led to increased numbers of neurons with elongated nuclei. We used conditional alleles for Lmnb1 and Lmnb2 to create forebrain-specific knockout mice. The forebrain-specific Lmnb1- and Lmnb2-knockout models had a small forebrain with disorganized layering of neurons and nuclear shape abnormalities, similar to abnormalities identified in the conventional knockout mice. A more severe phenotype, complete atrophy of the cortex, was observed in forebrain-specific Lmnb1/Lmnb2 double-knockout mice. This study demonstrates that both lamin B1 and lamin B2 are essential for brain development, with lamin B1 being required for the integrity of the nuclear lamina, and lamin B2 being important for resistance to nuclear elongation in neurons.
authors: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. coffinie@ucla.edu
authors: Catherine
authors: C
authors: Coffinier
authors: Hea-Jin
authors: HJ
authors: Jung
authors: Chika
authors: C
authors: Nobumori
authors: Sandy
authors: S
authors: Chang
authors: Yiping
authors: Y
authors: Tu
authors: Richard H
authors: RH
authors: Barnes
authors: Yuko
authors: Y
authors: Yoshinaga
authors: Pieter J
authors: PJ
authors: de Jong
authors: Laurent
authors: L
authors: Vergnes
authors: Karen
authors: K
authors: Reue
authors: Loren G
authors: LG
authors: Fong
authors: Stephen G
authors: SG
authors: Young
mesh_terms: D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000196:embryology* / Q000254:growth & development*; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D034881:Nuclear Lamina; D016548:Prosencephalon / Q000002:abnormalities* / Q000254:growth & development
chemical_list: D034921:Lamin Type B