| First Author | Mori T | Year | 2003 |
| Journal | J Neuropathol Exp Neurol | Volume | 62 |
| Issue | 3 | Pages | 280-91 |
| PubMed ID | 12638732 | Mgi Jnum | J:104859 |
| Mgi Id | MGI:3612924 | Doi | 10.1093/jnen/62.3.280 |
| Citation | Mori T, et al. (2003) Increased vulnerability to focal ischemic brain injury in human apolipoprotein E4 knock-in mice. J Neuropathol Exp Neurol 62(3):280-91 |
| abstractText | Accumulating evidence suggests that among the 3 human apolipoprotein E (apoE) isoforms encoded by the human APOE gene, the e4 allele may act to exacerbate brain damage in humans and animals. This study aimed to compare the isoform-specific vulnerability conferred by human apoE to ischemic brain damage, using mice expressing human apoE isoforms (apoE2, apoE3, or apoE4) in place of mouse apoE, produced by the gene-targeting technique in embryonic stem cells (knock-in, KI). Homozygous human apoE2 (2/2), apoE3 (3/3), or apoE4 (4/4) KI mice were subjected to permanent focal cerebral ischemia by a modified intraluminal suture method. Twenty-four h thereafter, brain damage, (as estimated by infarct volume and neurologic deficit) was significantly worse in 4/4 KI mice versus 2/2 or 3/3 KI mice (p < 0.001 for each comparison), with no significant differences between 2/2 and 3/3 KI mice. Immunohistochemistry for human apoE expression revealed similar apoE distribution with no significant difference in the immunostaining intensity among the 3 lines of KI mice. Notably. increased expression of human apoE was detected in neurons and astrocytes in the peri-infarct area, and a punctate expression pattern was evident in the border between the infarct and peri-infarct areas in all KI mice subjected to ischemia. Taken together, our results show that apoE affects the outcome of acute brain damage in an isoform-specific fashion (apoE4 > apoE3 = apoE2) in genetically engineered mice. |
