Abstract
Purpose :
Armadillo Repeat Containing, X-linked 1 (Armcx1) is a protein of the outer mitochondrial membrane whose endogenous function is unclear. We previously showed that Armcx1 overexpression in retinal ganglion cells (RGCs) increases mitochondrial transport and promotes axonal regeneration and neuronal survival after an optic nerve injury. Here, we hypothesize that the endogenous function of Armcx1 is to control axonal growth during development.
Methods :
We generated an Armcx1conditional knock-out mouse line. To delete Armcx1 in RGCs directly after differentiation but before axonal growth Isl1-Cre mice were crossed with the Armcx1f/f mice. We and others have shown that the Isl1-Cre expression beings in E11. Embryos were obtained from mice at embryonic day 13 and axons were traced using the carbocyanine dye, Dil. They were then sectioned with vibratome horizontally so that sections were parallel to the path of the optic nerve.
Results :
Preliminary results show that when Armcx1 is deleted in the early stages of RGC axonal growth in Isl1-Cre; Armcx1f/f mice at embryonic day 13, RGC axons fail to reach the optic chiasm. This result suggests that the growth of RGC axons has been impaired due to the lack of Armcx1.
Conclusions :
Our data suggest that Armcx1’s endogenous function is to regulate RGC axonal growth during development. Ongoing work is investigating if Armcx1’s role is restricted to axonal initiation or growth rate by studying the development of RGC axons at later time points (E12 to E14) in Isl1-Cre; Armcx1f/f mice. Furthermore, the mitochondrial distribution will be studied in these mutants.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.