Figure 6. Ablation of Chop restores motor function and reduces demyelination in S63del mice.

A) Rotarod analysis of motor function showed that four month old S63del mice remain for 200 seconds less as compared to wt and Chop-null mice. Instead, S63del/Chop-null mice perform like wt mice. B) Semithin sections stained with toluidine blue are shown from P180 wt, S63del, Chop-null and S63del/Chop-null sciatic nerves. S63del nerves manifest hypomyelination and demyelinated fibers and onion bulbs. Although hypomyelination is not ameliorated in S63del/Chop-null nerves, the number of demyelinating fibers is significantly reduced (Table). Examples of pathological fibers from S63del or S63del/Chop-null nerves are shown magnified below. Arrows indicate demyelinated fibers, stars indicate onion bulbs; and arrowheads indicates remyelinating fibers. Bar = 15 μm in upper panels and 5 μm in the magnified panels below. C) S63del transgene expression was analyzed in rescued nerves by semi-quantitative RT-PCR. Digestion of the amplimer with Dpn II distinguishes wt (326 bp) from transgenic cDNA (244 and 82 bp fragments). D-H) BiP, CHOP and DOC1,6 and 4 expression was analyzed by quantitative RT-PCR and normalized to 18S rRNA. Note that transgene expression and BiP activation remain in S63del/Chop-null nerves, whereas CHOP is undetectable and DOC1 falls below wt levels. DOC6 and 4 are not induced in S63del-L nerves.