| First Author | Yamada A | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 7 | Pages | 102741 |
| PubMed ID | 34258564 | Mgi Jnum | J:350870 |
| Mgi Id | MGI:6827245 | Doi | 10.1016/j.isci.2021.102741 |
| Citation | Yamada A, et al. (2021) Derepression of inflammation-related genes link to microglia activation and neural maturation defect in a mouse model of Kleefstra syndrome. iScience 24(7):102741 |
| abstractText | Haploinsufficiency of EHMT1, which encodes histone H3 lysine 9 (H3K9) methyltransferase G9a-like protein (GLP), causes Kleefstra syndrome (KS), a complex disorder of developmental delay and intellectual disability. Here, we examined whether postnatal supply of GLP can reverse the neurological phenotypes seen in Ehmt1 (Delta/+) mice as a KS model. Ubiquitous GLP supply from the juvenile stage ameliorated behavioral abnormalities in Ehmt1 (Delta/+) mice. Postnatal neuron-specific GLP supply was not sufficient for the improvement of abnormal behaviors but still reversed the reduction of H3K9me2 and spine number in Ehmt1 (Delta/+) mice. Interestingly, some inflammatory genes, including IL-1beta (Il1b), were upregulated and activated microglial cells increased in the Ehmt1 (Delta/+) brain, and such phenotypes were also reversed by neuron-specific postnatal GLP supply. Il1b inactivation canceled the microglial and spine number phenotypes in the Ehmt1 (Delta/+) mice. Thus, H3K9me2 and some neurological phenotypes are reversible, but behavioral abnormalities are more difficult to improve depending on the timing of GLP supply. |
