DelK32-lamin A/C has abnormal location and induces incomplete tissue maturation and severe metabolic defects leading to premature death

• DOI: 10.1093/hmg/ddr534
• Publication Date: 2011-11-17T07:18:09Z
• Authors: Anne T. Bertrand; Laure Renou; Aurélie Papadopoulos; Maud Beuvin; Emmanuelle Lacène; Catherine Massart; Chris Ottolenghi; Valérie Decostre; Sophia Maron; Saskia Schlossarek; Marie-Elodie Cattin; Lucie Carrier; Marie Malissen; Takuro Arimura; Gisèle Bonne
• Keywords: LMNA; Nuclear lamina; Premature aging

The LMNA gene encodes lamin A/C intermediate filaments that polymerize beneath the nuclear membrane, and are also found in nucleoplasm an uncharacterized assembly state. They thought to have structural functions regulatory roles signaling pathways via interaction with transcription factors. Mutations been involved numerous inherited human diseases, including severe congenital muscular dystrophy (L-CMD). We created Lmna(ΔK32) knock-in mouse harboring a L-CMD mutation. Lmna(ΔK32/ΔK32) mice exhibited striated muscle maturation delay metabolic defects, reduced adipose tissue hypoglycemia leading premature death. level of mutant proteins was markedly lower Lmna(ΔK32/ΔK32), while wild-type were progressively relocated from nucleoplasmic foci rim during embryonic development, maintained foci. In liver adipocyte differentiation, expression ΔK32-lamin altered sterol element binding protein 1 (SREBP-1) transcriptional activities. Taken together, our results suggest relocation at lamina seems important for potentially by releasing its inhibitory function on factors, but not restricted SREBP-1. And importantly, patients should be investigated putative disorders.