Increase of c-Fos and c-Jun expression in spinal and cranial motoneurons of the degenerating muscle mouse (Scn8a(dmu)).
The degenerating muscle (dmu) mouse harbors a loss-of-function mutation in the Scn8a gene, which encodes the alpha subunit of the voltage-gated sodium channel (VGSC) Na(V)1.6. The distribution of c-Fos and c-Jun was examined in spinal and cranial motoneurons of the dmu mouse. In the cervical spinal cord, trigeminal motor nucleus (Vm), facial nucleus (VII), dorsal motor nucleus of the vagus (X), and hypoglossal nucleus (XII) of wild-type mice, motoneurons expressed c-Fos and c-Jun-immunoreactivity. The immunoreactivity in wild-type mice was mostly weak and localized to the nucleus of these neurons whereas in the spinal cord and brain stem of dmu mice motoneurons showed intense c-Fos and c-Jun-immunoreactivity. The number of c-Fos-immunoreactive motoneurons was dramatically elevated in the cervical spinal cord (wild type, 4.8 +/- 1.0; dmu, 17.3 +/- 1.6), Vm (wild type, 76.2 +/- 21.6; dmu, 216.9 +/- 30.9), VII (wild type, 162.4 +/- 43.3; dmu, 533.3 +/- 41.2), and XII (wild type, 58.2 +/- 43.3; dmu, 150.9 +/- 25.7). The mutation also increased the number of c-Jun-immunoreactive motoneurons in the cervical spinal cord (wild type, 1.6 +/- 0.8; dmu, 12.1 +/- 2.1), Vm (wild type, 41.4 +/- 18.0; dmu, 123.1 +/- 11.7), and X (wild type, 39.1 +/- 10.7; dmu, 92.8 +/- 17.8). The increase of these transcription factors may be associated with the uncoordinated and excessive movement of forelimbs and degeneration of cardiac muscles in dmu mice.
Ichikawa
Hiroyuki
H
Division of Oral and Craniofacial Anatomy, Tohoku University Graduate School of Dentistry, Sendai, Miyagi 980-8575, Japan. hiroichi@anat.dent.tohoku.ac.jp
Kano
Mitsuhiro
M
Shimizu
Yoshinaka
Y
Suzuki
Toshihiko
T
Sawada
Eri
E
Ono
Wako
W
Chu
Leona W G
LW
Côté
Patrice D
PD
D000818:Animals; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D051379:Mice; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009132:Muscles / Q000473:pathology*; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012886:Skull / Q000294:innervation* / Q000378:metabolism* / Q000473:pathology; D015222:Sodium Channels / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; C491046:Scn8a protein, mouse; D015222:Sodium Channels