| First Author | Ahlemeyer B | Year | 2012 |
| Journal | Dis Model Mech | Volume | 5 |
| Issue | 1 | Pages | 125-40 |
| PubMed ID | 21954064 | Mgi Jnum | J:180632 |
| Mgi Id | MGI:5306724 | Doi | 10.1242/dmm.007708 |
| Citation | Ahlemeyer B, et al. (2012) Deletion of a single allele of the Pex11beta gene is sufficient to cause oxidative stress, delayed differentiation and neuronal death in mouse brain. Dis Model Mech 5(1):125-40 |
| abstractText | Impaired neuronal migration and cell death are commonly observed in patients with peroxisomal biogenesis disorders (PBDs), and in mouse models of this diseases. In Pex11beta-deficient mice, we observed that the deletion of a single allele of the Pex11beta gene (Pex11beta(+/-) heterozygous mice) caused cell death in primary neuronal cultures prepared from the neocortex and cerebellum, although to a lesser extent as compared with the homozygous-null animals (Pex11beta(-/-) mice). In corresponding brain sections, cell death was rare, but differences between the genotypes were similar to those found in vitro. Because PEX11beta has been implicated in peroxisomal proliferation, we searched for alterations in peroxisomal abundance in the brain of heterozygous and homozygous Pex11beta-null mice compared with wild-type animals. Deletion of one allele of the Pex11beta gene slightly increased the abundance of peroxisomes, whereas the deletion of both alleles caused a 30% reduction in peroxisome number. The size of the peroxisomal compartment did not correlate with neuronal death. Similar to cell death, neuronal development was delayed in Pex11beta(+/-) mice, and to a further extent in Pex11beta(-/-) mice, as measured by a reduced mRNA and protein level of synaptophysin and a reduced protein level of the mature isoform of MAP2. Moreover, a gradual increase in oxidative stress was found in brain sections and primary neuronal cultures from wild-type to heterozygous to homozygous Pex11beta-deficient mice. SOD2 was upregulated in neurons from Pex11beta(+/-) mice, but not from Pex11beta(-/-) animals, whereas the level of catalase remained unchanged in neurons from Pex11beta(+/-) mice and was reduced in those from Pex11beta(-/-) mice, suggesting a partial compensation of oxidative stress in the heterozygotes, but a failure thereof in the homozygous Pex11beta(-/-) brain. In conclusion, we report the alterations in the brain caused by the deletion of a single allele of the Pex11beta gene. Our data might lead to the reconsideration of the clinical treatment of PBDs and the common way of using knockout mouse models for studying autosomal recessive diseases. |
