Identification of New Oligodendrocyte‐ and Myelin‐Specific Genes by a Differential Screening Approach

Abstract

We have isolated several new genes that are specifically expressed by oligodendrocytes in the CNS. This was achieved by differential screening of a rat spinal cord cDNA library with probes derived from normal and from oligodendrocyte‐free spinal cord mRNAs. Four of these genes are exclusively expressed by oligodendrocytes: Three of these are not related to known genes, whereas one encodes the myelin oligodendrocyte glycoprotein (MOG). Four other genes are expressed by oligodendrocytes as well as by Schwann cells. One gene codes for apolipoprotein D, which is thought to be involved in lipid metabolism. A second cDNA sequence codes for the recently identified galactosylceramide‐synthesizing enzyme UDP‐galactose:ceramide galactosyl‐transferase. The third gene encodes a small protein with four putative transmembrane domains that is related to a T‐lymphocyte‐specific membrane protein, MAL. The fourth gene encodes the rat homologue of the stearyl‐CoA‐desaturase 2 (SCD2) gene, which is specifically expressed in the nervous system and involved in the synthesis and regulation of long‐chain unsaturated fatty acids essential for myelination. Finally, we found that a member of the β‐tubulin family is highly expressed in oligodendrocytes as well as neurons. The identification of several new proteins that may play a role in myelin synthesis and sheath formation will lead to new insight into this complex mechanism.

Schizophrenia Breakdown in the Well-regulated Lifelong Process of Brain Development and Maturation

“…In normal brain, apolipoprotein D is found primarily in white matter oligodendrocytes (Navarro et al 1998;Ong et al 1999). Finally, in normal younger adults who are continuing to myelinate (Yakovlev and Lecours 1967;Benes et al 1994;Bartzokis et al 2001), brain apolipoprotein D is primarily localized in oligodendrocytes (Schaeren-Wiemers et al 1995;Navarro et al 1998;Kalman et al 2000) as is the case in the rodent CNS where a maturation-associated induction of the gene's expression has been reported (Ong et al 1999).…”

“…Glia synthesize, excrete, and express the gene for apolipoprotein D, suggesting a specific role for this molecule in membrane lipid metabolism and repair in the central nervous system (CNS) (Schaeren-Wiemers et al 1995;Kalman et al 2000;Patel et al 1995). Apolipoprotein D levels have been shown to be elevated in old age and in a number of other neuropathologic disorders such as Alzheimer's disease (Kalman et al 2000) and excitotoxic damage (Montpied et al 1999) in regionally specific patterns.…”

HLA-DQB1*0602 Determines Disease Susceptibility in a New “Humanized” Multiple Sclerosis Model in HLA-DR15 (DRB1*1501;DQB1*0602) Transgenic Mice

“…MOBP is a CNS myelinspecific protein that plays a role in stabilizing the myelin sheath (16). Northern blot analysis, in situ hybridization, immunochemistry, and immunoelectron microscopy (16,17) indicated that MOBP is expressed exclusively in CNS white matter and more particularly throughout compact myelin, predominantly at the major dense lines of myelin (16). The encephalitogenic potential of MOBP was demonstrated in H-2 b (18) and H-2 s (19,20) mice, and two separate studies of proliferative response to MOBP peptides (pMOBP) by PBL from MS patients and controls indicated that MOBP65-87 was the region most frequently recognized by MS patients T cells (18).…”

Myelin-Associated Oligodendrocytic Basic Protein: A Family of Abundant CNS Myelin Proteins in Search of a Function

“…Southern blotting analysis confi rmed that these cDNAs were splice variants derived from a single copy of the Mobp gene [3] . During this same period Schaeren-Wiemers et al [4] isolated two clones termed CNS1 and CNS3 which also demonstrated partial sequence identity to the cDNAs described by Yamamoto et al . [3] and to ftg -1.…”