| First Author | Rozmahel R | Year | 2002 |
| Journal | Neurobiol Aging | Volume | 23 |
| Issue | 2 | Pages | 187-94 |
| PubMed ID | 11804702 | Mgi Jnum | J:80624 |
| Mgi Id | MGI:2446429 | Doi | 10.1016/s0197-4580(01)00267-6 |
| Citation | Rozmahel R, et al. (2002) Normal brain development in PS1 hypomorphic mice with markedly reduced gamma-secretase cleavage of betaAPP. Neurobiol Aging 23(2):187-94 |
| abstractText | Presenilin 1-null mice die at birth from brain and skeletal developmental deformities due to disrupted Notch signaling. Presenilin 1-null mice also have severely reduced gamma-secretase cleavage of betaAPP. The assumption has been that facilitation of Notch signaling and betaAPP processing by presenilin 1 are analogous functions. Here we describe a presenilin 1-targetted mouse model that expresses extremely low levels ( approximately 1% of normal) of mutant PS1-M146L. Homozygous mice have significantly reduced viability due to a Notch-like phenotype. The animals that survive have severe axial skeletal deformities and markedly diminished gamma-secretase activity and accumulation of betaAPP-C100, but no obvious abnormalities in brain development. These results suggest that, in mice, a marked reduction of PS1-facilitated gamma-secretase activity is not detrimental to normal brain development. |
