| First Author | Wang Y | Year | 2022 |
| Journal | Cells | Volume | 11 |
| Issue | 17 | PubMed ID | 36078123 |
| Mgi Jnum | J:328987 | Mgi Id | MGI:7339489 |
| Doi | 10.3390/cells11172715 | Citation | Wang Y, et al. (2022) The Central Domain of MCPH1 Controls Development of the Cerebral Cortex and Gonads in Mice. Cells 11(17) |
| abstractText | MCPH1 is the first gene identified to be responsible for the human autosomal recessive disorder primary microcephaly (MCPH). Mutations in the N-terminal and central domains of MCPH1 are strongly associated with microcephaly in human patients. A recent study showed that the central domain of MCPH1, which is mainly encoded by exon 8, interacts with E3 ligase betaTrCP2 and regulates the G2/M transition of the cell cycle. In order to investigate the biological functions of MCPH1's central domain, we constructed a mouse model that lacked the central domain of MCPH1 by deleting its exon 8 (designated as Mcph1-Deltae8). Mcph1-Deltae8 mice exhibited a reduced brain size and thinner cortex, likely caused by a compromised self-renewal capacity and premature differentiation of Mcph1-Deltae8 neuroprogenitors during corticogenesis. Furthermore, Mcph1-Deltae8 mice were sterile because of a loss of germ cells in the testis and ovary. The embryonic fibroblasts of Mcph1-Deltae8 mice exhibited premature chromosome condensation (PCC). All of these findings indicate that Mcph1-Deltae8 mice are reminiscent of MCPH1 complete knockout mice and Mcph1-DeltaBR1 mice. Our study demonstrates that the central domain of MCPH1 represses microcephaly, and is essential for gonad development in mammals. |
