| First Author | Herms J | Year | 2004 |
| Journal | EMBO J | Volume | 23 |
| Issue | 20 | Pages | 4106-15 |
| PubMed ID | 15385965 | Mgi Jnum | J:93306 |
| Mgi Id | MGI:3056838 | Doi | 10.1038/sj.emboj.7600390 |
| Citation | Herms J, et al. (2004) Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members. EMBO J 23(20):4106-15 |
| abstractText | 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. |
