The Journal of Neuroscience, December 15, 2004, ():
CNS Myelin Paranodes Require Nkx6-2 Homeoprotein Transcriptional Activity for Normal Structure
J. Neurosci. Southwood et al.
24: 11215
Supplemental data
Files in this Data Supplement:
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Figure 1 - Deletion construct for Nkx6-2 null mice
(A) Genomic organization of mouse Nkx6-2 and details of the targeting construct. R5, Eco RV; B, Bam HI; B2, Bgl II; S, Sma I; black boxes, coding regions; white boxes, 5? and 3? untranslated regions.
(B) Eco RV digested-DNA from G418-resistant ES cell clones reveal 9 and 5 kb bands with 5? and 3? genomic probes, respectively.
(C) Northern blots of poly A+-selected RNA from brains of adult wild type (+/+) and heterozygous (+/-) mice hybridize to a Nkx6?2 exon 3 probe. The 5 kb band in Nkx6-2 null mice (-/-), corresponds to a lacZ-Nkx6-2 hybrid mRNA.
- supplemental material
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Figure 2 ? Model of ultrastructural abnormalities observed in Nkx6-2 null mice
(A) The schematic depicts salient ultrastructural features of a normal myelinated axon (Raine, 1984). A longitudinal section (top) shows the relationship between an axon (gray) and a myelin sheath (black) with paranodal cytoplasmic loops flanking the compact myelin internode at ?g? (see Figure 4g). An unfurled view of this sheath (bottom) is colored to distinguish compact myelin (dark pink) from cytoplasmic channels (pink). The trapezoid shape reflects the fact that lateral loops from the outer spiral wraps are closer to nodes of Ranvier than those of the inner wraps. Cross sections at vertical dashes (?b? and ?c?) illustrate internodal and paranodal myelin shown in Figure 4b and c, respectively.
(B) The schematic reflects abnormalities in Nkx6-2 null mice. Oligodendrocyte processes in the periaxonal space (black asterisk, Figure 4e)are likely derived from membrane protrusions of the myelin inner tongue process (at ?e?). Multilamellar myelin ?flaps? (black arrows, Figure 4f) are comprised of membrane leaflets that extend along the axon in-register and may stem from impeded elongation of myelin membrane (at ?f?). Failure of lateral loops to terminate at paranodes in Nkx6-2 null mice (Figure 4d, h) causes thin compact myelin (at ?d?), which stems from membrane scalloping of inner tongue processes (at ?h?). The organization of myelin loops at the lateral edges of myelin flaps (horizontal dotted lines to the right) is unknown.
