Development of myelination in optic tract of the cat.

The postnatal development of myelin in the optic nerve and tract of normal and dark reared cats has been studied quantitatively with light and electron microscopy. In the newborn cat few myelinated fibers (3% of the population) are seen in the optic tract. Until the end of the second postnatal week, the total number of myelinated axons in the tract remains low (23%). At this time, however, there is an explosive increase in the rate of myelination and by the end of the fourth postnatal week 80% of the optic tract axons have acquired a myelin sheath. Thereafter, the number of myelinated axons increases gradually, reaching adult levels (100%) at 12 weeks. During the initial period of myelination, the average axon diameter is 0.6 mu for unmyelinated fibers and a.2 mu for myelinated fibers. Both of these means remain substantially unchanged until myelination is completed, suggesting that initial myelination of an axon is not a continuous process but rather proceeds in a step-wise manner. Dark rearing appears to have no effect on the initiation of myelination.     

Postnatal differentiation of the rat trochlear nerve

A morphometric analysis of postnatal differentiation in the rat trochlear nerve was studied by light and electron microscopy as an initial basis for understanding motor unit heterogeneity in the extraocular muscles (EOM). A total of 35 animals were examined 7–90 days postnatal (dpn). The mean number of fibers increased from 222 at 7 dpn to 274 in the adult and the size distribution became bimodal at 21 dpn. In the adult 17% of the myelinated fibers had a mean diameter of 2.5 μm and 83% were 7.3 μm. The estimated number of unmyelinated axons decreased from about 40% at 7 dpn to 20% at 14 dpn and 16% in the adult. The myelinated fiber diameter was more highly correlated with age and body weight than was fiber number. Certain organelles characteristic of active membrane growth were present in the Schwann cell cytoplasm at the paranode region. Redundant loops were prominent at 10 dpn, when many axons were still in Schwann cell bundles. During the third postnatal week a number of alterations were noted which may reflect a loss of polyneuronal innervation. These included thicker myelin sheaths and ultrastructural evidence of axonal degeneration. Branching of myelinated fibers was limited to the intramuscular portions of the nerve at 18 dpn. The g-ratio of the largest fibers at selected ages was nearly constant at .71 and was correlated with fiber diameter (r = 0.40), except at 14 dpn. The periodicity of the myelin sheath had either an inverse or constant relationship to the number of lamellae. The significance of the results is discussed in relation to postnatal development, the size principle and heterogeneity in the EOM motor units.     

Myelination in the human hippocampal formation from midgestation to adulthood

Myelination, one of the last steps of neuronal development, was examined in the human fetal and postnatal hippocampal formation using immunohistochemistry to detect a protein component of the myelin sheath, the myelin basic protein synthesized by oligodendroglial cells. Myelin basic protein-immunoreactive oligodendroglial cells were first seen at the 20th gestational week in the fimbria fornicis and in the alveus. Between the 21st and 35th weeks, myelinated axons also appeared in the fimbria fornicis. At the age of 39 gestational weeks, short and thin myelinated fibers were present in the fimbria, in the alveus, and less so in the stratum oriens of the hippocampus, while the first oligodendroglial cells appeared in the stratum lacunosum-moleculare and in the hilus. By the 2nd postnatal week myelinated fibers appeared in the stratum lacunosum-moleculare of Ammon's horn. At the 3rd month, myelination was strong in the alveus, moderate in the strata oriens, lacunosum-moleculare and radiatum of Ammon's horn, while only a small number of myelinated fibers were detected in the hilus. By the 5th month, the first oligodendroglial cells were detected in the molecular layer of the dentate gyrus. Myelination continued in the following years, particularly in the dentate gyrus, where even at the age of 11 years the density of myelinated fibers did not reach the adult level. It appears that the first myelinated axons belong to the long-projecting large hippocampal pyramidal cells and/or to their subcortical and cortical afferents. The sequence of myelination follows the known developmental pattern of hippocampal afferent and efferent pathways, and the prolonged myelination might be a factor in the prolonged functional maturation of hippocampal circuitry.     

P2, P1, and P0 myelin protein expression in developing rat sixth nerve: a quantitative immunocytochemical study

Myelination and the expression of myelin proteins P2, P1, and P0 were studied quantitatively in the rat sixth cranial nerve during development. The postnatal development and growth of all myelin sheaths in this nerve have been studied morphometrically in a companion paper. Epon-embedded blocks with closely matched topography in the transverse plane were selected from rats perfused at ages 1-4, 8, 15, and 20 days. From each block, serial semithin sections were cut, etched, and immunostained according to the peroxidase-antiperoxidase method with well-characterized polyclonal antisera that reacted specifically with P0 glycoprotein and the basic proteins P1 and P2. The immunoreactivities of individual myelin sheaths were measured by densitometry. Numbers of compact myelin lamellae, myelin spiral lengths, and axon diameters were determined on electronmicrographs of adjacent thin sections. At birth anti-P0 immunoreactivity was found on sheaths with two and more compact lamellae; neither P1 nor P2 immunoreactivity was observed. On day 2, myelin sheaths with five and eight lamellae were stained respectively by anti-P1 and anti-P2. On day 3 the percentages of myelin sheaths stained were substantially higher: P0 95%, P1 78%, P2 15%. By day 4, anti-P0 and anti-P1 immunoreactivity was present in 95% of myelin sheaths; 35% were stained by anti-P2. For P2, staining intensity and percentage of myelin sheaths stained continued to increase and by day 20, 85% were anti-P2-positive. The density of immunoreactivity was not uniform in all myelin sheaths. At young ages staining varied with all three proteins. The variability decreased as myelin sheaths thickened; it persisted longest for anti-P2. We conclude that the density and distribution of immunoreactivities of P0, P1, and P2 reflect their relative concentrations during myelin sheath development and growth. We attribute lack of detectable anti-P2 immunoreactivity in some small sheaths at 20 days to their early stage of myelination and also to limitations of the method. We infer from our observations that all myelin-forming Schwann cells express P2 basic protein.     

Impaired myelination of the human hippocampal formation in Down syndrome

Myelination is considered as one of the last steps of neuronal development and is essential to the physiologically matured function of afferent and efferent pathways. In the present study, myelin formation was examined in the human fetal, postnatal and adult hippocampal formation in Down syndrome and in age-matched controls with immunohistochemistry detecting a protein component of the myelin sheath, the myelin basic protein synthesized by oligodendroglial cells. Myelination is mainly a postnatal event in the hippocampal formation of both healthy controls and in patients with Down syndrome. In patients with Down syndrome the sequence of myelination of the hippocampal formation followed a similar developmental pattern to that in controls. However, myelin formation was generally delayed in Down syndrome compared to age-matched controls. In addition, in the hilus of the dentate gyrus a decreased density of myelinated axons was detected from the start of myelination until adulthood. The majority of local axons (mossy fibers) are not myelinated in the hilar region and myelinated fibers arriving in the hilus come mainly from the subcortical septal nuclei. Since intact septo-hippocampal connections are necessary for memory formation, we hypothesize that decreased myelination in the hilus may contribute to the mental retardation of Down syndrome patients.     

Multiply myelinated axons in the optic nerve of mice deficient for the myelin-associated glycoprotein

We recently reported that some retinal ganglion cell axons in mice deficient for the myelin-associated glycoprotein are concentrically surrounded by more than one myelin sheath. In the present study, we demonstrate that myelin sheaths displaced from the axon reveal a normal ultrastructure of compact myelin, with the only exception that multiple myelination of axons frequently correlates with the presence of unfused regions of major dense lines. Supernumerary sheaths terminated on other sheaths or on astrocyte cell surfaces in a pattern closely resembling the morphology of a true paranode. The thickness of compact myelin of multiply myelinated axons was significantly increased when compared with axons of similar caliber surrounded by a single myelin sheath. Our observations demonstrate that maintenance of compact myelin and paranodal regions is not dependent on direct axonal contact and that the presence of more than one concentric myelin sheath around an axon results in dysregulation of the axon-to-fiber ratio. © 1995 Wiley-Liss, Inc.     

A correlative light and electron microscopic study of postnatal myelination in the murine corpus callosum

Oligodendroglial cells differ in their ultrastructural appearance depending on their myelin producing and maintaining activity. To better understand the relationship between light and electron microscopic features of myelination, myelin formation in the corpus callosum was studied in young postnatal mice. Immunostaining for myelin basic protein (MBP), which has an important role in myelin compaction, was compared with conventional Luxol Fast Blue myelin staining and with electron microscopic images of unlabeled tissue. MBP-immunostaining labeled a few oligodendroglial cells at postnatal day (P)3, and a few axons at P7 in the corpus callosum, below the fronto-parietal somatosensory cortex. By P10 there were more myelinated axons below the somatosensory cortex and the first MBP-immunoreaction appeared in the cingulum: labeling appeared even later in the remaining areas of corpus callosum. Electron microscopy revealed numerous medium oligodendroglial cells at P7 in the corpus callosum, below the somatosensory cortex with the first sign of myelination at P10. By P14, there were numerous myelin sheaths with loosely built structure, and the number of myelin sheaths increased continuously thereafter. However, even as late as P28, the presence of both thick, compact and thin, loosely structured myelin sheaths in the same section suggested ongoing myelination. With Luxol Fast Blue myelin staining was first observed in the corpus callosum relatively late, at P14. Areal differences in myelination of the corpus callosum, seen with MBP-immunohistochemistry, indicate that myelin formation follows cortical maturation rather than the rostro-caudal developmental growth of the corpus callosum. Myelination of the afferent and efferent fibers within the cortical areas seems to follow the inside-out maturational pattern of cortical neurons, with the first myelinated axons always appearing in layers V-VI. In addition to the known neuronal and astroglial factors that regulate myelin formation by oligodendroglial cells, we suggest that these cells and their myelin covering may also influence axonal maturation. Light microscopic data obtained with MBP-immunohistochemistry correlates well with electron microscopic observations but not with Luxol Fast Blue staining which reveals myelinated axons only relatively late in development. Therefore, both MBP-immunostaining and electron microscopy are useful, alone or in combination, for the detection of myelination, demyelination as well as remyelination processes in animal models and also in humans.     

Development of the pyramidal tract in the hamster. II. An electron microscopic study

We undertook a qualitative and quantitative electron microscopic study of the growth and development of the pyramidal tract in the hamster to investigate the mode of growth of the axons, the possibility of fiber degeneration during development, and the process of myelination. By calculating the total fiber number as the product of axon density and tract area for several postnatal ages, we found that the pyramidal tract grows through the medulla as a compact bundle containing nearly twice the number of fibers as the mature tract. During the second postnatal week there is a substantial loss of axons followed in the third and fourth weeks by a more gradual loss such that by 34 days after birth the total number of axons reaches the adult value. Myelination in the hamster pyramidal tract begins at 7 days and continues at a very slow rate until the third postnatal week, when a dramatic increase in myelin formation occurs. By 34 days after birth the number of myelinated axons is approximately 80% that of the adult. As has been reported for other CNS tracts, there does not seem to be a “critical diameter” of an axon that absolutely determines the presence or absence of myelin on a fiber. However, all axons above 0.5 μm in diameter are myelinated at approximately the same rate, while those under this diameter are myelinated much more slowly and even in the adult make up only a small percentage of the total myelinated fibers.     

Rat optic nerve: electrophysiological, pharmacological and anatomical studies during development

Changes in conduction properties and in morphology were studied during rat optic nerve growth from birth (when no myelin is present and the glia have not differentiated) to adulthood (when the optic nerve is essentially 100% myelinated). Myelination begins around the sixth postnatal day and proceeds rapidly so that 85% of the fibers are myelinated at 28 days of age. Mean diameter of optic nerve axons remains about 0.2 micron for the first week and then increases rapidly if the fiber is being myelinated. Those axons not being myelinated remain about 0.2-0.3 micron in diameter. At birth the compound action potential has a single negative peak and a conduction velocity of about 0.2 m/s. The increase in conduction velocity prior to myelination is considerably greater than can be accounted for on the basis of increase in axonal diameter. There is no clear step increase in the velocity of the shortest latency peak correlated with the onset of myelination. During myelination the compound action potential develops multiple short latency components, which evolve into the adult-like 3 component compound action potential by 3-4 weeks of age. Durations of the relative refractory period and supernormal period decrease as age increases, but are not related to myelination in a simple manner. Sodium appears to be the only significant carrier of inward current at all ages. A measureable calcium conductance is not present at any age. Voltage-dependent potassium conductance contributes to the compound action potential at all ages, but the response to 4-aminopyridine in rapidly conducting fibers is apparently smaller than that in slowly conducting fibers. These results show that conduction can occur before myelination or the differentiation of glial cells. Moreover, changes in conduction velocity do not depend entirely on myelination or increases in axonal size. Finally, these results suggest a reorganization of axonal membrane properties during the development of rat optic nerve.     

The growth and myelination of central and peripheral segments of ventral motoneurone axons. A quantitative ultrastructural study.

This study compares the growth and myelination of those parts of cervical ventral motoneurone axons in the spinal cord (the intramedullary segments) and in the ventral roots of fetal and young rats (up to 21 days postnatal). The same fibre bundles are examined centrally and peripherally. Myelination begins centrally and peripherally at about birth. However, the peripheral segments of some fibres may begin to become myelinated before the central. Over the first 3 weeks after birth the minimum circumference of peripheral segments of myelinated axons remains relatively constant at 3 mum but that of central segments falls from 2.5 mum to just over 1 mum. Axons within the same fibre bundles tend to be thinner and less heavily myelinated centrally than peripherally. With ageing, axon circumference becomes more strongly correlated with sheath thickness. The thickness of the sheath surrounding an axon of a given circumference does not differ statistically from one age to another or between central and peripheral segments. Studies of myelin sheath growth rate show that in the early stages glial and Schwann cells vary independently of one another in the rates at which they add new turns to sheaths around central and peripheral segments of axons in the same bundles.     

Growth pattern of axons in the optic nerve of chick during myelogenesis

The purpose of this experiment was to study the diameter of axons at the time of the initiation of myelin and the pattern of growth of axons in the optic nerve of the chick. Embryos between 15 and 20 days and chicks 3, 5, 22 and 60 days of age were studied on the electron microscopic level. Based on axon diameter a unimodal distribution of unmyelinated axons is present through day 20 of incubation with a mean of approximately 0.35 micrometer. This population is represented through 22 days of age but from day 3 on, a second distinct population of unmyelinated axons is present which has a mean diameter that is approximately twice that of the smaller unmyelinated axons. All axons do not increase simultaneously in diameter but once growth starts, the unmyelinated axons apparently double in diameter at a relatively rapid rate prior to myelination. On incubation day 17 less than 1% of the axons in the optic nerve is myelimated. The number of axons in this group and their diameter (mean approximately 1.2 micrometer) remain relatively constant through day 3 but from days 5 through 22, two distinct populations of myelinated axons are present. By day 60, three distinct distributions of myelinated axons are present with mean diameters of 0.51 micrometer, 1.76 micrometer, and 3.90 micrometer. These populations represent approximately 20%, 67%, and 13% respectively of the total fiber population. As age increases the diameter of some myelinated axons is as small as or smaller than the unmyelinated axons at an earlier period in development. This suggests that factors other than axon diameter might be involved in the start of myelination. It appears that the increase in axon diameter does not occur in a continuous manner but in a saltatory manner from one size to another.     

The optic nerve of the viper, Vipera aspis

A quantitative investigation of the optic nerves of eight adult vipers was carried out, both at the level of resolution of the light microscope by stereological methods, and at the level of resolution of the electron microscope. The majority (87%) of axons are myelinated, and the fibers are organized in fascicles; each bundle of axons is disposed around a central column of glial cells of which the greater proportion (62%) are oligodendrocytes, 33% are astrocytes and the remaining 5% are microglial cells. Estimations of the total number of fibers varied, from 5.37 X 10(4) to 6.96 X 10(4), among the eight specimens. The distribution of diameters of myelinated fibers is well characterized (chi 2 = 16.84, df = 22, 0.9 greater than p greater than 0.5) by a three-parameter lognormal distribution with a mean of 0.735 micron, standard deviation of 0.239 micron, and origin of 0.21 micron. Axon diameter is linearly related (r = 0.60) to the number of electron-dense layers in the myelin sheath. The diameters of unmyelinated fibers are distributed (chi 2 = 1.95, df = 4, 0.9 greater than p greater than 0.5) as a two-parameter lognormal distribution with mean of 0.25 micron and standard deviation of 0.067 micron. A surprisingly large number of myelinated fibers, apparently dispersed at random throughout the nerve, showed anomalies of myelination; two possible explanations, between which it is impossible to discriminate on the basis of the available data, are offered for this state of affairs.     

A quantitative electron microscopic study of myelination in the pyramidal tract of rat

The ultrastructure of fibers during myelin formation in the pyramidal tract of rats is described. The distribution of fiber classes based on counts of myelin lamellae was determined for newborn, young and mature rats. In newborn rats (2–12 days), growth of the axon was extremely rapid in fibers undergoing early myelination, resulting in greater variation in the relation between axon circumference and sheath thickness and, also, in the presence of myelin sheaths that were unusually thin in relation to the size of the axons. In young rats (12 days to 8 weeks), the numbers of myelin lamellae present in the sheaths increased in proportion to the increase in axon circumference. In adult rats, the numbers of myelin lamellae present in the sheaths was in linear relation to axon circumference for all sizes of myelinated fibers. Approximately 20% of the fibers were nonmyelinated. The number of glia cells per axon at the onset of myelination was approximately 20% of the adult ratio. During growth, myelination gliosis resulted in a steady increase in the number of glia cells per axon until adult levels were ultimately achieved. Our observations suggest that formation of myelin lamellae by oligodendroglia cells may be controlled by the caliber of the axon.     

Endurance exercise does not modify nerve fibre morphology in the rat soleus nerve

The effects of exercise on the myelination and growth of axons in the nerve to the soleus muscle (NSM) was investigated in young male Wistar rats. Experimental animals were run on a treadmill for 13 weeks (70 min/day, 6 days/week), while sedentary weight-matched animals of the same age and sex served as controls. The activity of the enzymes, phosphofructokinase (PFK) and succinate dehydrogenase (SDH) were measured in the soleus muscle to assess the effects of training on the anaerobic glycolytic and oxidative capacities. Axon and myelin sheath cross-sectional areas were measured from electron micrograph montages of the whole NSM with the aid of a digitizing tablet.The exercise programme produced large adaptive increases in the capacity of the soleus muscle for both oxidative and anaerobic glycolytic metabolism. The specific activity of PFK and SDH increased in the soleus muscle of exercised animals by 42.8% and 68.2%, respectively. In the NSM, however, there were no differences between control and exercised animals concerning the total number of myelinated nerve fibers, the size of axons and myelin sheaths of nerve fibres and the degree of myelination of axons (myelin area divided by axon area).Comparison with other studies suggests that the intensity of exercise may be the critical parameter responsible for discrepancies in the literature. Reports suggesting that exercise increases the size of nerve fibres should not be generalized to all exercise programmes.     

Trigeminal alveolar nerve of the lower jaw in the cichlid Tilapia mariae: evidence for continual axon generation and presence of exceptionally small myelinated axons

Cross sections from the trigeminal alveolar nerve of the lower jaw in the cichlid Tilapia mariae were examined by electron microscopy. The nerve fibers are arranged in groups with a core of unmyelinated and small myelinated axons, surrounded by myelinated axons of varying sizes. The core contains large bundles of unmyelinated axons collectively ensheathed by circumferentially located Schwann cells, as well as smaller bundles of unmyelinated axons partly separated from each other by Schwann cell processes. Among the unmyelinated axons, occasional scattered profiles resembling growth cones are seen. The total number of axons in this tooth-related nerve increases from approximately 1,500 to 5,000, as the animals grow in length from 4.5 to 21.5 cm. Some 24-49% of the axons are unmyelinated. The myelinated axons have maximum diameters of 1.0-3.0 micron, depending on body size. Most myelinated axons have diameters less than 1.0 micron and the smallest ones reach down to 0.3 micron. These results show that there is a continual addition of axons to the alveolar nerve of the lower jaw in Tilapia mariae and that the critical diameter for myelination in this peripheral nerve is similar to that typically found in the mammalian CNS.     

Quantitative studies on myelinated and unmyelinated nerve fibres in the interatrial septal region of aged rat hearts

Intracardiac nerve fibres from the interatrial septum were studied quantitatively and qualitatively by electron microscopy of transversely sectioned nerve bundles in male Wistar rats of 4 and 24 months. No significant changes were found in the myelinated fibre diameters, myelinated axon diameters, myelin sheath thicknesses, g ratios, myelinated fibre areas, unmyelinated axon diameters and unmyelinated axon areas. However, there was evidence of structural changes to the nerve fibres and Schwann cells at 4 and 24 months, increasing in prevalence with age: some myelinated fibres showed infolds, disruptions and clefts of the myelin sheath and accumulation of electron dense myelin-like fragments in the axoplasm. Unmyelinated axons showed fewer changes in structure but also contained similar fragments in the axoplasm. The numbers of neurotubules and neurofilaments per microm2 in unmyelinated intracardiac axons was significantly greater than in those in samples of the cervical vagal trunk. This may be an adaptation to the continuous mechanical stress experienced by these intracardiac nerves. It is concluded that there is little structural evidence to suggest that the conductive properties of intracardiac nerve fibres are adversely affected in aged rats.     

Transplantation of oligodendrocyte progenitor cells into the rat retina: Extensive myelination of retinal ganglion cell axons

In most mammals, retinal ganglion cell axons are unmyelinated in the retina. The same axons become myelinated in the optic nerve. Various studies suggest that retinal ganglion cell axons are also in principle, myelination competent intraretinally and that non-neuronal factors at the retinal end of the optic nerve prevent the migration of oligodendrocyte progenitor cells into the retina. To test this hypothesis directly, we injected oligodendrocyte progenitor cells into the retina of young postnatal rats. We observed massive myelination of ganglion cell axons in the retina 1 month after cell transplantation. Electron microscopic analysis revealed that intraretinal segments of ganglion cell axons were surrounded by central nervous system myelin sheaths with a normal morphology. Our results thus provide direct evidence for the myelination competence of the intraretinal part of rat retinal ganglion cell axons. © 1996 Wiley-Liss, Inc.     

Nerve growth factor enhances regeneration through silicone chambers

The effect of exogenous NGF on axonal growth across a gap between sectioned ends of a sciatic nerve within silicone chambers was examined in Sprague-Dawley rats. After nerve section and surgical implantation, silicone chambers were filled with either a 1 mg/ml nerve growth factor (NGF)/saline solution (experimental) or a normal saline solution (control). Four weeks after surgery, the regenerated nerves from within the silicone chambers were dissected and fixed for histological studies at both light microscopic and ultrastructural levels. Morphological analysis of the nerves showed no difference between the NGF-treated and control groups in the size of the regenerated nerves within the chambers or in the diameters of myelinated axons. Total myelinated axonal counts were determined from within the distal chamber. NGF significantly increased the number of myelinated axons that grew into the distal end of the chamber (2126 +/- 437 NGF/saline; 1064 +/- 268 saline; P less than 0.05 Student's t test). Counts of the unmyelinated axons from the distal nerve segment from the two groups were not different. Myelin sheath thickness was 58% greater in the NGF-treated group compared with that in the saline group. There was no difference between the two groups in the size-frequency spectra of the diameters of the myelinated axons in the distal segment. The NGF/saline group showed a more mature-appearing regenerated nerve based on the percentage of myelinated axons, thickness of the myelin sheaths, and development of internal organization (e.g., amount of endoneurial collagen fibers, ensheathment of unmyelinated axons by Schwann cells, and interfascicular patterns).(ABSTRACT TRUNCATED AT 250 WORDS)     

Retinal abnormalities in the Siamese cat

An electron microscope examination of the optic nerve of the opossum, Didelphis marsupialis aurita, indicates a total count of 74,7000 fibers of which approximately 20% are unmyelinated. The diameters of myelinated fibers ranged from 0.5-7 mum (mode at 1.25 mum) and those of the unmyelinated fibers ranged from 0.25-2.25 mum (mode at 0.75 mum). Myelinated and unmyelinated fibers are uniformly distributed throughout the nerve. Myelin sheath structure is similar to that described in other species and are formed by 2 to 17 myelin rings (mode at 6). There is a good correlation (r = 0.92) between axon and myelin areas. The relation between myelin thickness and axons diameter shows a wide distribution with a peak at 0.77.     

Hypomyelinated mutant mice IV: Peripheral myelin injp

This study compares peripheral myelination in a specific subdivision of the sciatic nerve ofjp^msd and unaffected littermate mice. No significant differences are found in numbers of myelinated and unmyelinated axons, diameters of axons, thickness of myelin sheaths relative to axon diameter, extent of unmyelinated axon segregation by Schwann cell processes, or in the ultrastructure of myelin and Schwann cells. By contrast,jp^msd mutant mice show severe CNS hypomyelination. This evidence, that thejp^msd mutation affects only oligodendrocytes, distinguishes mutations at this locus from others producing CNS hypomyelination in which PNS myelin is also affected.