Fig. 1.
Fbs2;Ngly1 dKO mice are viable and have normal motor function. (A) The role of FBS2 and NGLY1 in the ERAD pathway. SCFFBS2 recognizes the innermost positions of high mannose-type glycans of misfolded glycoproteins and ubiquitinates the glycoproteins. NGLY1 removes N-glycans from glycoproteins in which the N-glycosylated Asn (N) are converted to Asp (D) prior to degradation by the proteasome. (B and C) Body weights of Fbs2;Ngly1 dKO male (B) and female (C) mice. Mice were weighed at weekly intervals after weaning. Values represent means ± SD. The number of mice weighed is noted in parentheses. Statistical significance among four groups was determined using one-way ANOVA. n.s., not significant. (D) Suppression of embryonic lethality of Ngly1-KO mice by Fbs2 deletion. The ratios of observed to expected frequencies of progeny obtained by crossing of Fbs2−/+;Ngly1−/+ mice are shown. Refer to SI Appendix, Table S1 for actual count. (E) Fbs2;Ngly1 dKO mice, like wild-type mice, exhibited no sign of abnormal hindlimb clasping when suspended by the tail. Left shows Fbs2 KO male (control, 25 wk); right shows Fbs2;Ngly1 dKO male (25 wk). Compare with the example of the mouse exhibiting typical hindlimb clasping in SI Appendix, Fig. S1C. (F and G) Rotarod testing of motor coordination of male (F) and female (G) mice at 5 wk of age. The time until the mouse dropped from the accelerating rod (4.5 to 45 rpm in 4 min) is shown. Values represent means ± SD. The number of mice examined is shown in parentheses. Statistical significance among four groups was determined using one-way ANOVA. n.s., not significant.