Reciprocal Knock-in Mice to Investigate the Functional Redundancy of Lamin B1 and Lamin B2

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2014 Mar 28

PMID 24672053

Citations 19

Authors

John M Lee

Yiping Tu

Angelica Tatar

Daniel Wu

Chika Nobumori

Hea-Jin Jung

Yuko Yoshinaga

Catherine Coffinier

Pieter J de Jong

Loren G Fong

Stephen G Young

Affiliations

Soon will be listed here.

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.

Citing Articles

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