Homology between human Chromosome 2p13.3 and the wobbler
critical region on mouse Chromosome 11: comparative high-resolution
mapping of STS and EST loci on YAC/BAC contigs
Karin Resch,* Dirk Korthaus,* Niels Wedemeyer,** Andreas Lengeling,† Melanie Ronsiek, Cora Thiel,
Kristin Baer,§ Harald Jockusch, Thomas Schmitt-John
Developmental Biology Unit, W7, University of Bielefeld, D-33501 Bielefeld, Germany
Received: 13 April 1998 / Accepted: 26 June 1998
Abstract. Human Chr 2p13-14 and homologous regions on
mouse Chrs 6 and 11 have been subjects of previous studies be-
cause they comprise the loci for several neuromuscular diseases.
Here we report on high-resolution mapping of 55 STS and EST
loci on human Chr 2p13.3 and of 47 markers on the corresponding
region on proximal mouse Chr. 11. The maps comprise several
known genes, MEIS1/Meis1, RAB1a/Rab1a, MDH1/Mor2,
OTX1/Otx1, and REL on human 2p13.3 and mouse Chr 11, re-
spectively, as well as the wobbler (wr) critical region of the mouse.
Whereas a perfect correspondence was found in most of the 4-Mb
region, a small rearrangement was discovered around the OTX1/
Otx1 locus. The detailed STS and EST transcript maps of these
regions and a further narrowing down of the mouse wr critical
region to the interval between D11Mit79 and D11Mit19 allow for
the selection of positional candidate genes for wr, and the exclu-
sion of others.
Having reached an advanced stage of gene mapping, the Human
Genome Project provides valuable information for positional clon-
ing of disease genes in other species, in particular the mouse, a
model species for neurological disorders (for example, weaver
Patil et al. 1995). Human Chr 2p13-14 and homologous regions
on mouse Chr 6 and 11 have been subjects of previous studies
because they comprise the loci for several neuromuscular diseases,
such as human limb girdle muscular dystrophy type 2b (LGMD2B;
Bashir et al. 1996) and Miyoshi Myopathy (MM; Bejaoui et al.
1995) and mouse mutations wobbler (wr, Chr 11; Kaupmann et al.
1992) and motor neuron degeneration 2 (mnd2, Chr 6; Jones
et al. 1993). Genes in the wobbler region of mouse Chr 11 have
human orthologs on the distal sub-band 2p13.3, while the mnd2
region of Chr 6 corresponds to the proximal sub-band 2p13.1
(Mammalian Homology and Comparative Maps, http://
A homology relation between human and mouse diseases has
previously been excluded for LGMD2B and wobbler (Korthaus et
al. 1997) by radiation hybrid (RH) mapping as well as for
LGMD2B and mnd2 (Bashir et al. 1996) by STS mapping. New
human segregation data (Weiler et al. 1996; Illarioshkin et al.
1997) indicate that phenotypically different cases of the neuromus-
cular diseases, LGMD2B-like and MM-like, are caused by the
same mutation. Nevertheless, at least three independent neuromus-
cular disease genes must be located in a relatively small region of
about 50 cR as approximated by RH mapping (Korthaus et al.
Our interest is focused on the wr mutation of the mouse and
therefore especially on the homology relation between human Chr
2p13.3 and proximal mouse Chr 11. In addition to a degeneration
of motor neurons, the wobbler disease of the mouse comprises a
defect in spermiogenesis. As shown by chimera experiments, these
two cellular phenotypes seem to be autonomously expressed in the
respective organs, spinal cord and testis, indicating the affected
gene(s) must be expressed in those (Augustin et al. 1997).
The wr gene maps close to the genes for cytoplasmic malate
dehydrogenase (Mor2 in mouse; Korthaus et al. 1996) and for the
small GTP-binding protein Rab1a (Wedemeyer et al. 1996); its
identity is not yet known. A wr critical interval between the gene
for the EGF receptor (Egfr) and the microsatellite D11Mit19 has
previously been defined by segregation analysis (Kaupmann et al.
1992; Wedemeyer et al. 1996; Korthaus et al. 1996).
Here we report on comparative high-resolution mapping of
STS and EST loci on YACs from human Chr 2p13.3 and on YACs
and BACs from the corresponding region on proximal mouse Chr
11. The maps comprise several known genes, coding for the tran-
scription factors MEIS1 (Moskow et al. 1995) and OTX1 (Kastury
et al. 1994; Acampora et al. 1996), the reticuloendotheliosis proto-
oncogene REL (Brownell et al. 1985), the small GTP-binding
protein RAB1a, and the cytoplasmic malate dehydrogenase, on
human 2p13.3 and mouse Chr 11 respectively, as well as the
wobbler (wr) critical region of the mouse.
Materials and methods
Mouse strains and segregation analysis.
For the origin of the Mus
musculus C57BL/6J-wr stock and for genetic segregation analysis of Mus
spretus SEG/1, see Kaupmann and associates (1992).
An interspecies backcross (Mus musculus C57BL/6J-wr×Mus spretus
× Mus musculus C57BL/6-wr was used in addition to an intra-
species backcross (Mus musculus C57BL/6J-wr × Mus musculus AKR/N)
× Mus musculus C57BL/6-wr.
YAC and BAC library screening and DNA preparations.
and human YACs were isolated by screening different YAC libraries with
markers mapping to mouse Chr 11 and human Chr 2p13.3, respectively,
and had the following designations: ymWIBR119H3, ymWIBR117B8,
* These authors contributed equally to this work.
** Present address: Max-Planck-Institute for Molecular Genetics, Ihnes-
trasse 73, D-14195 Berlin, Germany
† Present address: Dept. of Psychiatry, Center for Neurobiology and Be-
havior, University of Pennsylvania, 415 Curie Boulevard, Philadelphia,
Pennsylvania 19104, USA
§ Present address: Institute for Pharmacology, Winterthurerstrasse 190,
CH-8057 Zu¨rich, Switzerland
Correspondence to: T. Schmitt-John
Mammalian Genome 9, 893–898 (1998).
© Springer-Verlag New York Inc. 1998