Splicing Pattern, Transcript Start Distribution,
and DNA Sequence of the Mouse Gene (Mobp)
Encoding Myelin-Associated Oligodendrocytic
Basic Protein
A. S. McCallion, G. J. Stewart, P. Montague,* I. R. Griffiths,*
and R. W. Davies
1
University of Glasgow, Institute of Biomedical and Life Sciences (IBLS), Division of Molecular
Genetics, Anderson College, 54 Dumbarton Road, Glasgow G11 6NU, Scotland; and *Applied
Neurobiology Group, Department of Veterinary Clinical Studies, University of Glasgow,
Bearsden, Glasgow G61 1QH, Scotland, United Kingdom
We have cloned the mouse gene
Mobp,
encoding the
family of myelin-associated oligodendrocytic basic pro-
teins (MOBP), to facilitate elucidation of its genomic
organization and regulation. We report near complete
sequence analysis of the
Mobp
gene (G11 kb), including
complete sequence of all exons and their associated
splice junctions. The
Mobp
gene comprises eight discrete
exons and encompasses a genomic region in excess of 15
kb. We provide a definitive analysis of the alternative
splicing events and exon usage required in the generation
of the reported splice variants of
Mobp
transcripts. We
identify sequences corresponding to the coding regions
of all reported protein isoforms. Consequently, we demon-
strate that sequence regions, predicted to encode unique
portions of two putative protein isoforms in the rat (MOBP
71 and MOBP 99), are not fully conserved between the rat
and the mouse: we predict that the mouse equivalents are
two distinct polypeptides of 73 amino acids, MOBP73A
and MOBP73B, respectively. We have analyzed sequence
from 63 oligo-capped, cloned cDNA fragments and identify
six transcription start points associated with the
Mobp
gene at postnatal day 26. This study provides the platform
for a more detailed analysis of the function of the
Mobp
gene product and subsequent evaluation of its possible
involvement in known neuropathies.
INTRODUCTION
Myelin-associated oligodendrocytic basic protein
(MOBP) is a newly recognized major CNS-specific
myelin component, which is present throughout com-
pact myelin. It has been suggested that MOBP may play
a role in compacting or stabilizing the myelin sheath
(Yamamoto et al., 1994; Holz et al., 1996; Montague et al.,
1997), possibly by binding the negatively charged acidic
phospholipids of the cytoplasmic membrane. MOBPhas
been shown to localize in the MDL of compact CNS
myelin (Yamamoto et al., 1994).
Six splice variants have been identified which are
predicted to encode five different protein isoforms of
MOBP (Yamamoto et al., 1994; Holz et al., 1996). In the
rat, these are predicted to be 69, 71, 81, 99, and 170
amino acids long, respectively, proline rich, and basic.
Though all isoforms thus far identified (Yamamoto et al.,
1994; Holz et al., 1996; Montague et al., 1997) have amino
acid residues 1–68 in common, they differ in the length
and polarity of their respective C-terminal regions(Holz
et al., 1996; Montague et al., 1997). These protein iso-
forms are encoded by a single gene, Mobp. Six different
mRNA splice variants have been reported based on
cDNA sequence data (Yamamoto et al., 1994; Holz et al.,
1996). It was not known whether these represented all
splice variants, or how the mRNAsplice variants related
to protein isoforms. RNA splicing provides a potential
site of regulation of the occurrence of particular protein
1
To whom correspondence and reprint requests should be ad-
dressed. Fax: 0141 330 5102. E-mail: gbga21@udcf.gla.ac.uk.
MCN
Molecular and Cellular Neuroscience
13, 229–236 (1999)
Article ID
mcne.1999.0745,
available online at http://www.idealibrary.com on
229
1044-7431/99 $30.00
Copyright
1999 by Academic Press
All rights of reproduction in any form reserved.