Originally published as Genetics Published Articles Ahead of Print on June 18, 2005.

Genetics, Vol. 171, 185-196, September 2005, Copyright © 2005
doi:10.1534/genetics.105.043208

Molecular Genetic Analysis of the Nested Drosophila melanogaster Lamin C Gene

Sandra R. Schulze, Beatrice Curio-Penny, Yuhong Li, Reza A. Imani, Lena Rydberg, Pamela K. Geyer and Lori L. Wallrath¹

Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242

¹ Corresponding author: Department of Biochemistry, 3136 MERF, University of Iowa, Iowa City, IA 52242.
E-mail: lori-wallrath{at}uiowa.edu

Lamins are intermediate filaments that line the inner surface of the nuclear envelope, providing structural support and making contacts with chromatin. There are two types of lamins, A- and B-types, which differ in structure and expression. Drosophila possesses both lamin types, encoded by the LamC (A-type) and lamin Dm₀ (B-type) genes. LamC is nested within an intron of the essential gene ttv. We demonstrate that null mutations in LamC are lethal, and expression of a wild-type LamC transgene rescues lethality of LamC but not ttv mutants. Mutations in the human A-type lamin gene lead to diseases called laminopathies. To determine if Drosophila might serve as a useful model to study lamin biology and disease mechanisms, we generated transgenic flies expressing mutant LamC proteins modeled after human disease-causing lamins. These transgenic animals display a nuclear lamin aggregation phenotype remarkably similar to that observed when human mutant A-type lamins are expressed in mammalian cells. LamC aggregates also cause disorganization of lamin Dm₀, indicating interdependence of both lamin types for proper lamina assembly. Taken together, these data provide the first detailed genetic analysis of the LamC gene and support using Drosophila as a model to study the role of lamins in disease.

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