TY - JOUR
T1 - Disruption of the polyubiquitin gene Ubb causes retinal degeneration in mice
AU - Lim, Daehan
AU - Park, Chul Woo
AU - Ryu, Kwon Yul
AU - Chung, Hyewon
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/5/21
Y1 - 2019/5/21
N2 - We have previously demonstrated that a reduction in ubiquitin (Ub) levels via disruption of the polyubiquitin gene Ubb results in reactive gliosis and hypothalamic neurodegeneration in mice. However, it is not known whether other neural tissues, apart from the brain, can also be affected by Ubb disruption. We examined the retina, which, being derived from the diencephalon, has the same developmental origin as the hypothalamus. We found that expression levels of Ubb were much higher than those of the other polyubiquitin gene Ubc in the retina. In retinal tissues from Ubb knockout (KO) mice, we found that Ubc expression was upregulated to compensate for the loss of Ubb; however, the Ub pool remained disrupted, with reduced levels of free Ub. To directly demonstrate whether the disrupted Ub pools affect neural integrity in retinal tissues, we investigated retinal layers in control and Ubb KO mice. Using optical coherence tomography and histological analysis, we demonstrated that the thickness of the outer nuclear layer of the retina was decreased in Ubb KO mice compared to control mice, suggesting that retinal degeneration was induced by Ub deficiency. Furthermore, the mRNA and protein levels of rhodopsin decreased and those of glial fibrillary acidic protein increased in Ubb KO mouse retinas. Therefore, the maintenance of Ub pools in the retina appears to be crucial for the survival of photoreceptor cells and the prevention of excessive glial cell activation.
AB - We have previously demonstrated that a reduction in ubiquitin (Ub) levels via disruption of the polyubiquitin gene Ubb results in reactive gliosis and hypothalamic neurodegeneration in mice. However, it is not known whether other neural tissues, apart from the brain, can also be affected by Ubb disruption. We examined the retina, which, being derived from the diencephalon, has the same developmental origin as the hypothalamus. We found that expression levels of Ubb were much higher than those of the other polyubiquitin gene Ubc in the retina. In retinal tissues from Ubb knockout (KO) mice, we found that Ubc expression was upregulated to compensate for the loss of Ubb; however, the Ub pool remained disrupted, with reduced levels of free Ub. To directly demonstrate whether the disrupted Ub pools affect neural integrity in retinal tissues, we investigated retinal layers in control and Ubb KO mice. Using optical coherence tomography and histological analysis, we demonstrated that the thickness of the outer nuclear layer of the retina was decreased in Ubb KO mice compared to control mice, suggesting that retinal degeneration was induced by Ub deficiency. Furthermore, the mRNA and protein levels of rhodopsin decreased and those of glial fibrillary acidic protein increased in Ubb KO mouse retinas. Therefore, the maintenance of Ub pools in the retina appears to be crucial for the survival of photoreceptor cells and the prevention of excessive glial cell activation.
KW - Degeneration
KW - Outer nuclear layer
KW - Photoreceptor
KW - Retina
KW - Ubiquitin
UR - http://www.scopus.com/inward/record.url?scp=85063524375&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2019.03.164
DO - 10.1016/j.bbrc.2019.03.164
M3 - Article
C2 - 30935687
AN - SCOPUS:85063524375
SN - 0006-291X
VL - 513
SP - 35
EP - 40
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -