Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members

The EMBO Journal
Jochen HermsUlrike Müller

Abstract

The Alzheimer's disease beta-amyloid precursor protein (APP) is a member of a larger gene family that includes the amyloid precursor-like proteins, termed APLP1 and APLP2. We previously documented that APLP2-/-APLP1-/- and APLP2-/-APP-/- mice die postnatally, while APLP1-/-APP-/- mice and single mutants were viable. We now report that mice lacking all three APP/APLP family members survive through embryonic development, and die shortly after birth. In contrast to double-mutant animals with perinatal lethality, 81% of triple mutants showed cranial abnormalities. In 68% of triple mutants, we observed cortical dysplasias characterized by focal ectopic neuroblasts that had migrated through the basal lamina and pial membrane, a phenotype that resembles human type II lissencephaly. Moreover, at E18.5 triple mutants showed a partial loss of cortical Cajal Retzius (CR) cells, suggesting that APP/APLPs play a crucial role in the survival of CR cells and neuronal adhesion. Collectively, our data reveal an essential role for APP family members in normal brain development and early postnatal survival.

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Citations

Sep 21, 2011·Experimental Brain Research·Dorothee AydinUlrike C Müller
Sep 29, 2011·Experimental Brain Research·Timo Wagner, Claus U Pietrzik
Nov 1, 2011·Experimental Brain Research·Collin Y Ewald, Chris Li
Nov 17, 2011·Experimental Brain Research·Donat KögelChristian Behl
Nov 29, 2011·Experimental Brain Research·Johannes ProxPaul Saftig
Feb 22, 2012·Experimental Brain Research·Ulrike C MüllerThomas Deller
Nov 27, 2007·Acta Neuropathologica·Charles DuyckaertsBenoît Delatour
Apr 25, 2009·Acta Neuropathologica·Thomas Arendt
Mar 17, 2011·Brain Structure & Function·Marijke A M LemmensChristoph Schmitz
Apr 17, 2008·Molecular Neurobiology·Hyang-Sook Hoe, G William Rebeck
Mar 14, 2009·Proceedings of the National Academy of Sciences of the United States of America·Maria StanteTommaso Russo
Sep 22, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hongmei LiHui Zheng
Sep 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yi XueYa Ha
Aug 10, 2010·The Journal of Biological Chemistry·Hongmei LiHui Zheng
Apr 2, 2009·The Journal of Biological Chemistry·Matthias GralleFred S Wouters
Jul 25, 2008·The Journal of Biological Chemistry·Gopal Thinakaran, Edward H Koo
Apr 7, 2009·Cerebral Cortex·Orly ReinerTamar Sapir
Feb 23, 2012·Cold Spring Harbor Perspectives in Medicine·Ulrike C Müller, Hui Zheng
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Apr 17, 2012·International Journal of Alzheimer's Disease·Daniel A Bórquez, Christian González-Billault
Oct 19, 2006·Neuro-degenerative Diseases·Brigitte Anliker, Ulrike Müller
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Jan 11, 2011·Molecular Brain·Yun-wu ZhangHuaxi Xu
Aug 23, 2012·PloS One·Maya A KoikeFrank M LaFerla

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