1 Genetics Division, Brigham and Women's Hospital, Harvard Medical School,
Boston, MA 02476, USArr
2 National Human Genome Research Institute, National Institutes of Health,
Bethesda, MD 02115, USA
3 Department of Genetics, Washington University, St. Louis, MO 20892, USA
4 Department of Biomedical Engineering, Cleveland Clinic Foundation, Cleveland,
OH 44195, USA
Author for correspondence (e-mail:
beier{at}rascal.med.harvard.edu)
Accepted 22 May 2003
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SUMMARY |
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Key words: ADAMTS, White-spotting, Melanocyte migration, Mouse
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Introduction |
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The white-spotting mutations, which affect the maturation and survival of
neural crest-derived melanoblasts, have been particularly enlightening
regarding the developmental mechanisms required for normal lineage
determination, migration and proliferation. Notable among these was the
determination that the tyrosine kinase receptor Kit is mutated in
dominant spotting (W) and its ligand stem cell factor (Scf;
Kitl - Mouse Genome Informatics) is the gene mutated in steel mice
(Sl). Studies of the lethal spotting (ls) and piebald
(s) mouse mutants, which are characterized by mutations in endothelin
3 (Edn3) and its G-protein coupled receptor endothelin-B receptor
(Ednrb), respectively, illustrate the obligatory requirement for
endothelin-signaling in pigment cell development similar to that of
Scf/Kit (Baynash et al.,
1994; Hosoda et al.,
1994
). Abnormalities in the transcription factor Mitf
results in the microopthalmia (mi) mutation
(Hodgkinson et al., 1993
) and
a defect in the sry-related homeobox gene Sox10 results in dominant
megacolon (Dom) (Southard-Smith
et al., 1998
). Recent studies have shown how these signaling
pathways intersect (Potterf et al.,
2000
; Wu et al.,
2000
).
The belted (bt) locus is one of the few 'classic' white-spotting
mutations yet to be characterized. It presents as a mostly pigmented mouse
except for a region proximal to the hindlimbs that appears as a white belt.
The first allele of this mutation was identified in 1945
(Murray and Snell, 1945) and
many additional alleles have been identified. Skin-neural tube recombination
experiments provided conflicting results regarding the embryonic cell type
that is defective during development
(Mayer and Maltby, 1964
;
Schaible, 1972
). These studies
were re-interpreted by Silvers in light of Mintz's hypothesis about the clonal
development of melanoblast precursors; Silvers concluded that bt mice
have a number of unviable melanoblast clones, most of which are replaced by
melanoblasts migrating from neighboring viable clones. However, the belt
region remains non-pigmented because it is growing too rapidly to be
repopulated (Silvers,
1979
).
We report that bt is due to a defect in a novel ADAMTS (a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type I motif) protein, which is a member of a large family of secreted metelloproteases that are presumed to interact with the extracellular matrix (ECM). The gene encoding a homologous and highly similar protease, GON-1, has been shown to play a crucial role in cell migration in C. elegans. Our results suggest this function has been conserved in mammalian development. Notably, our analysis demonstrates that the bt gene product is not made by melanocytes themselves, but rather by the mesenchyme through which these cells migrate. This result implies that there is a highly coordinated and dynamic pattern of gene expression in the developing embryo that is required for the proper localization of neural-crest-derived cells.
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Materials and methods |
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Physical mapping
Screening of two YAC libraries identified one clone of 300 kb that
contained the flanking microsatellite markers. Using these markers as anchors,
a contig of BAC clones was established by BAC walking. Three contig BAC clones
were obtained by screening a 129/Sv BAC library (Genome Systems, St Louis, MO)
with PCR-amplified STSs from adjacent BAC clone ends. All STS fragments were
mapped using either mouse radiation hybrids or a C57BL/6J x M.
spretus backcross to ensure their appropriate map location. The contig
was confirmed by direct sequencing of BAC clones using STS-specific primers.
HindIII digests of the three BAC clones revealed a similar
restriction pattern suggesting a substantial overlap between them. The BAC-end
sequences were used to generate oligonucleotide probes, and filters containing
spotted clones from the RPCI-23 B6 library was hybridized using the 'overgo'
strategy (Ross et al., 1999).
Twelve clones were identified and STS-content mapped and three clones were
sequenced (RP23-24F24, Accession Number AC084384; RP23-5K17, Accession Number,
AC084382; RP23-54K18, Accession Number AC084385)
(Fig. 1).
|
Expression analysis
Northern analysis was done using the Origene Multi-tissue PolyA+ Northern
blot (Origene) and the Mouse Embryo MTN blot (Clontech). Hybridization was
carried out with the probes Adex 3/8 and TS20mid3'F/2R (described above)
using standard techniques. For in situ analysis, FVB/NJ mouse embryos were
fixed overnight in 4% paraformaldehyde in PBS. Date of plug formation was
noted as E 0.5. Reverse transcribed digoxigenin-conjugated probes were made
from linearized plasmids, DCT cDNA (Steel
et al., 1992) and Adex3/8. Whole-mount in situ hybridizations were
performed using published protocols
(Wilkinson and Nieto, 1993
)
with modifications as detailed elsewhere
(Loftus et al., 2002
). In situ
hybridization analysis on tissue sections were done using standard techniques
as previously described (Somerville et
al., 2003
).
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Results |
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The assignment of bt to distal mouse chromosome 15 was already
known from previous mapping studies
(Silvers, 1979). To determine
the precise location by high-resolution-mapping, homozygous bt mice
were crossed with wild-type DBA/2J and M. castaneus (CAST) mice and
their F1 bt/+ progeny were intercrossed or backcrossed. The
homozygous bt offspring were analyzed using microsatellite markers
from distal mouse chromosome 15. As CAST mice are more distantly related to B6
than are DBA/2J, the frequency of polymorphism in the B6xCAST cross was
higher, which has allowed us to define at high resolution the
bt-containing interval. Several unresolved microsatellite markers
closely linked to bt were ordered by using DNA from a reference cross
between B6 and M. spretus, the EUCIB backcross panel
(European Backcross Collaborative Group,
1994
).
In the analysis of over 1500 meioses, we identified five recombinants between D15Mit108 and D15Mit272, the microsatellite markers most closely flanking the bt locus. No recombinants were found between bt and D15Mit 245. Using these markers as anchors, a contig of BAC clones derived from a 129/Sv genomic library covering the interval was established as described in the Materials and methods. Single-strand conformational polymorphism (SSCP) analysis of the recombinants using primers derived from BAC end-sequence narrowed the interval carrying the mutation further (Fig. 2).
|
BLAST analysis of the genomic sequence identified a region with homology to the ADAMTS family of metalloproteases. No other homologies to sequences in the non-redundant or EST databases were identified. Primers corresponding to an internal part of the presumptive transcript were designed and an RT-PCR product was generated from mouse embryonic and skin mRNA. Northern analysis using this probe identified a transcript in embryonic polyA-containing mRNA (see below). A 4644 bp full-length transcript was identified using 5' and 3' RACE. This contained a 1425 amino acid open reading frame, most closely related to the human ADAMTS9 gene (Fig. 3). In consultation with the Mouse and Human Gene Nomenclature Committees (www.informatics.jax.org/mgihome/nomen/ and www.gene.ucl.ac.uk/nomenclature/), this novel family member has been designated Adamts20.
|
Northern analysis of poly-A-containing mRNA from adult tissue showed barely detectable expression in skin only (data not shown). Analysis of embryonic mRNA identified a major transcript of 8 kb that increased in abundance from day E11 to E17 (Fig. 4), as well as two additional bands at E17. In situ hybridization analysis of whole-mount embryos revealed a highly dynamic pattern of expression (Fig. 5). Specifically, Adamts20 expression in the neural tube is visible at E9.5-11.5. This precedes expression of the melanoblast marker DCT, which is expressed in the developing pigmented retinal epithelium of the eye at E9.5 and in migrating melanoblasts at E10.5. By E11.5 Adamts20 expression has extended laterally from the neural tube along the sides of the embryo with increased density surrounding the base of the limb buds. Again, this expression of Adamts20 precedes expression of DCT detected in migrating melanoblasts in the same region, which are visible at E12.5 but not at E11.5.
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Discussion |
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Analysis of Adamts20 using the simple modular architecture
research tool
(http://smart.embl-heidelberg.de/)
reveals that it has the protein motifs found in other family members,
including a propeptide typical in length of the ADAMTS family, a
reprolysin-type catalytic domain, a disintegrin-like domain, an ADAMTS
cystein-rich domain, a spacer devoid of cysteines and a TS repeat (TSR1)
(Hurskainen et al., 1999). The
C-terminal region of ADAMTS-20A, the short product of Adamts20,
contains an additional eight TS domains; the long product ADAMTS-20B, which is
generated by an alternatively spliced mRNA, carries six more TS domains (for a
total of 14). While this paper was in review, the independent identification
of mouse Adamts20 was reported
(Llamazares et al., 2003
).
This corresponds to the long product we have identified. Expression of this
gene in adult tissue was analyzed using northern and western analysis, and
found primarily in brain and testes. Metalloprotease activity was demonstrated
using a peptide substrate.
The ADAMTS protease family comprises 19 distinct gene products that are
also present in invertebrates. Like most secreted metalloproteases, the ADAMTS
enzymes are secreted as pro-enzymes, which are activated in the secretory
pathway or at the cell surface by pro-protein convertases such as furin.
Important functions in development and in human disease have been ascertained
for some of these enzymes. ADAMTS1, ADAMTS4 and ADAMTS5 are believed to
mediate loss of cartilage aggrecan in arthritis
(Tortorella et al., 1999).
ADAMTS13 mutations cause inherited thrombocytopenic purpura
(Levy et al., 2001
), and
autoantibodies to this enzyme may be the cause of acquired forms of the
disease. Mutations in ADAMTS2 in humans cause a severe inherited skin
fragility (Ehlers-Danlos syndrome type VIIC or dermatosparactic type) that was
first detected in a variety of animal species and termed dermatosparaxis
(Colige et al., 1999
;
Nusgens et al., 1992
).
As is the case for all white-spotting mutants, the melanocyte deficiency
found in bt mice may be the result of any of a number of mechanisms,
including the disruption of neural crest formation, specification of the
melanoblast lineage, proliferation, survival, migration throughout the embryo,
migration from dermis to epidermis, entry into the hair follicle or
differentiation into any of the various stages of melanocyte development.
Adamts20bt/Adamts20bt
mice are unique among the classic spotting mutants in several ways. First, the
mouse mutants that have early effects on melanocyte development such as
Ednrbs/Ednrbs and
Edn3ls/Edn3ls demonstrate more
extensive ventral spotting than dorsal spotting
(Dunn and Charles, 1937). This
is thought to be due to an early reduction in melanoblast numbers that fail to
proliferate and migrate sufficiently to populate the entire embryos, thus
leaving the furthest migratory portions devoid of melanoblasts
(Pavan and Tilghman, 1994
).
However,
Adamts20bt/Adamts20bt
mice demonstrate a more pronounced dorsal than the ventral spotting,
suggesting that this mutation acts later in development. Furthermore, in
addition to exhibiting regional defects in hair pigmentation,
KitW/+, ScfSl/+,
Ednrbs/Ednrbs, Ednrbs/+,
Edn3ls/Edn3ls and
Edn3ls/+ mice have a reduction of melanocytes in hardarian
gland, membraneous labyrinth, choroids, leg musculature and ankle skin,
indicating a widespread defect in melanocyte function. However
Adamts20bt/Adamts20bt
mice have a melanocyte reduction restricted only in the hair follicles in the
white belt region, suggesting a more restricted mode of action. Taken together
with the presumptive role of Adamts20 as a metalloprotease, these
findings suggest that Adamts20bt disrupts a
melanocyte developmental pathway that is unique from those described for other
spotting mutations.
Mayer and Maltby (Mayer and Maltby,
1964) have examined the etiology of white-spotting in
Adamts20bt mice using embryonic grafting
experiments. Areas of skin from presumptive white spotted and pigmented areas
of E12-12.5
Adamts20bt/Adamts20bt
embryos were grafted into coelom of the chick and allowed to form skin and
hair. Grafts obtained from presumptive pigmented areas developed pigmented
hairs and melanocytes in the dermis of the graft and in the coelom of the
host. However, most grafts from white spotted regions displayed unpigmented
hairs, yet had extensive melanocytes in the dermis between the follicles and
in the coelom, suggesting neural crest-derived melanocytes could function
normally in supportive environments. Mayer and Maltby concluded that the
melanoblasts were able to occupy the entire skin graft from the white spotted
area but were unable to form differentiated melanocytes within the hair
follicles in this region. They propose that
Adamts20bt mutation acts at the hair follicle to
either not allow entry of melanoblasts or to not support their differentiation
into functioning melanocytes within the follicular environment. Our
observation that Adamts20 is expressed in the developing dermis at
E13.5 and in hair follicles at later embryonic ages is consistent with this
conclusion. However, as previously noted, other investigators obtained
conflicting results in similar experiments
(Schaible, 1972
), and Silvers
has suggested that the results obtained in both studies could be due to
effects on the progenitor melanoblast population
(Silvers, 1979
).
The potential role of Adamts20 may perhaps be best inferred from
the analysis of distal tip cell (DTC) migration in C. elegans
(reviewed by Lehmann, 2001).
During larval development, the gonad acquires two U-shaped arms by directed
migration of DTCs along the body wall basement membranes. The specific path of
migration is controlled positively and negatively by several guidance factors,
including netrins and TGF
homologs. However, no DTC migration occurs in
the absence of the gon-1 gene product, which has been shown to be a
ADAMTS family member with remarkable homology to Adamts20 (37% amino
acid identity and 50% similarity; Fig.
3). (Blelloch and Kimble,
1999
). ClustalW analysis reveals that Adamts20 and the
highly similar Adamts9 proteins are more closely related to the
GON-1 product than they are to other members of the ADAMTS family,
which is remarkable given their evolutionary distance
(Fig. 3). Genomic sequence
analysis predicts the existence of a highly related Drosophila
protein GH1639p, although nothing has yet been reported regarding its
expression or function. The possible role of Adamts20 in the
regulation of migration is consistent with the observation that its closest
mammalian homolog, ADAMTS-9, is located at the cell surface and can process
versican, a large aggregating proteoglycan that has been implicated in neural
crest cell migration (Somerville et al.,
2003
). One notable distinction between the proposed conservation
of the role of these ADAMTS family proteases in the regulation of cell
migration is that GON-1 is expressed by the migrating DTCs, while
Adamts20 is not expressed in migrating melanocytes. However,
GON-1 is also expressed in muscle and has a role in determining gonad
shape, demonstrating that this protease does have a non-cell autonomous
function in C. elegans (Blelloch
et al., 1999
; Blelloch and
Kimble, 1999
).
Secreted metalloproteinases could be required for cell migration by virtue
of a relatively nonspecific modification of the ECM such that it is permissive
for cell transit. Alternatively, metalloproteinases may be required for
specific processing of secreted guidance factors. This is of particular
significance, given the well-characterized roles of secreted factors such as
Scf and Edn3 in melanoblast migration. Of note is the fact
that two mutant Kit alleles, Wsash and
Wbanded, have a belt when heterozygous. Both of
these mutations show ectopic expression of Kit during embryogenesis
due to genomic rearrangements (Duttlinger
et al., 1993; Kluppel et al.,
1997
). It has been suggested that this ectopic expression might
sequester soluble SCF, reducing the amount of ligand available to migrating
melanoblasts and reducing their survival by a non-cell autonomous mechanism.
The possible role of secreted metalloproteases in developmental regulation is
supported by evidence that the induction of matrix metalloproteinase 9 (MMP9)
in bone marrow cells results in the release of soluble SCF
(Heissig et al., 2002
). The
authors conclude that this enables bone marrow repopulating cells to
translocate to a permissive vascular niche, favoring differentiation and
reconstitution of the stem/progenitor cell pool.
In situ analysis of Adamts20 expression during embryogenesis
reveals a remarkably dynamic pattern of expression. Given this dramatically
changing pattern, one might expect that a mutation in Adamts20 would
have a more severe embryonic phenotype. The mild phenotype found in
bt mutant mice may be due to functional redundancy within the ADAMTS
metalloprotease family. However, it is notable that all of the mutations found
in the bt mice are well downstream of the metalloprotease domain.
These secreted mutant proteins may therefore retain partial activity, and the
bt mutation may thus represent a hypomorphic rather than a null
phenotype. A counterpoint to this argument is the evidence from other ADAMTS
mutations that suggests these alleles could also result in a near complete
loss of function. Naturally occurring mutations in ADAMTS2 and ADAMTS13 cause
amino acid changes in the ancillary domains of the respective proteases, yet
there is near complete or complete loss of function
(Levy et al., 2001).
Additionally, analysis of the processing of aggrecan by ADAMTS4 and versican
by ADAMTS9 provides biochemical evidence that the protease domains do not
function in the absence of the ancillary domains
(Tortorella et al., 2000
;
Somerville et al., 2003
).
Ultimately, an engineered null mutation of Adamts20 will be necessary
to address these possibilities.
Finally, the rapidly changing pattern of Adamts20 expression during development implies a tightly regulated signaling interaction between the tissues that express this protease and the population of cells whose migration it influences. It will be of considerable interest to identify the substrates for this enzyme whose proteolysis presumably underlies the belted phenotypes, as well as the transcriptional mechanisms that facilitate the coordinated expression during melanoblast migration of Adamts20 and other signaling molecules such as Kit and Scf.
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ACKNOWLEDGMENTS |
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Footnotes |
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REFERENCES |
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---|
Baynash, A. G., Hosoda, K., Giaid, A., Richardson, J. A., Emoto, N., Hammer, R. E. and Yanagisawa, M. (1994). Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Cell 79,1277 -1285.[Medline]
Beier, D. R., Morton, C. C., Leder, A., Wallace, R. and Leder, P. (1989). Perinatal lethality (ple): A mutation caused by integration of a transgene into distal mouse chromosome 15. Genomics 4,498 -504.[Medline]
Blelloch, R., Anna-Arriola, S. S., Gao, D., Li, Y., Hodgkin, J. and Kimble, J. (1999). The gon-1 gene is required for gonadal morphogenesis in Caenorhabditis elegans. Dev. Biol. 216,382 -393.[CrossRef][Medline]
Blelloch, R. and Kimble, J. (1999). Control of organ shape by a secreted metalloprotease in the nematode Caenorhabditis elegans. Nature 399,586 -590.[CrossRef][Medline]
Colige, A., Sieron, A. L., Li, S. W., Schwarze, U., Petty, E., Wertelecki, W., Wilcox, W., Krakow, D., Cohn, D. H., Reardon, W. et al. (1999). Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene. Am. J. Hum. Genet. 65,308 -317.[CrossRef][Medline]
Dickie, M. M. (1954). Expanding knowledge of the genome of the mouse. J. Natl. Cancer Inst. 15, 679.
Dunn, L. C. and Charles, D. (1937). Studies on
spotting patterns. Genetics
22, 14-42.
Duttlinger, R., Manova, K., Chu, T. Y., Gyssler, C., Zelenetz,
A. D., Bachvarova, R. F. and Besmer, P. (1993). W-sash
affects positive and negative elements controlling c-kit expression: ectopic
c-kit expression at sites of kit-ligand expression affects melanogenesis.
Development 118,705
-717.
European Backcross Collaborative Group (1994). Towards high resolution maps of the mouse and human genomes - a facility for ordering markers to 0.1 cM resolution. Hum. Mol. Genet. 3,621 -627.[Abstract]
Haldane, J. B. S., Sprunt, A. D. and Haldane, N. M. (1915). Reduplication in mice. J. Genet. 5, 133-135.
Heissig, B., Hattori, K., Dias, S., Friedrich, M., Ferris, B., Hackett, N. R., Crystal, R. G., Besmer, P., Lyden, D., Moore, M. A. et al. (2002). Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109,625 -637.[Medline]
Hodgkinson, C. A., Moore, K. J., Nakayama, A., Steingrimsson, E., Copeland, N. G., Jenkins, N. A. and Arnheiter, H. (1993). Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell 74,395 -404.[Medline]
Hosoda, K., Hammer, R. E., Richardson, J. A., Baynash, A. G., Cheung, J. C., Giaid, A. and Yanagisawa, M. (1994). Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. Cell 79,1267 -1276.[Medline]
Hurskainen, T. L., Hirohata, S., Seldin, M. F. and Apte, S.
S. (1999). ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of
a new family of zinc metalloproteases. General features and genomic
distribution of the ADAM-TS family. J. Biol. Chem.
274,25555
-25563.
Kluppel, M., Nagle, D. L., Bucan, M. and Bernstein, A.
(1997). Long-range genomic rearrangements upstream of Kit
dysregulate the developmental pattern of Kit expression in W57 and Wbanded
mice and interfere with distinct steps in melanocyte development.
Development 124,65
-77.
Lehmann, R. (2001). Cell migration in invertebrates: clues from border and distal tip cells. Curr. Opin. Genet. Dev. 11,457 -463.[CrossRef][Medline]
Levy, G. G., Nichols, W. C., Lian, E. C., Foroud, T., McClintick, J. N., McGee, B. M., Yang, A. Y., Siemieniak, D. R., Stark, K. R., Gruppo, R. et al. (2001). Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 413,488 -494.[CrossRef][Medline]
Llamazares, M., Cal, S., Quesada, V. and Lopez-Otin, C. (2003). Identification and characterization of ADAMTS-20 defines a novel subfamily of metalloproteinases-disintegrins with multiple thrombospondin-1 repeats and a unique GON-domain. J. Biol. Chem. 31,31 .
Loftus, S. K., Larson, D. M., Baxter, L. L., Antonellis, A.,
Chen, Y., Wu, X., Jiang, Y., Bittner, M., Hammer, J. A., 3rd and Pavan, W.
J. (2002). Mutation of melanosome protein RAB38 in chocolate
mice. Proc. Natl. Acad. Sci. USA
99,4471
-4476.
Matesic, L. E., Yip, R., Reuss, A. E., Swing, D. A., O'Sullivan,
T. N., Fletcher, C. F., Copeland, N. G. and Jenkins, N. A.
(2001). Mutations in Mlph, encoding a member of the Rab effector
family, cause the melanosome transport defects observed in leaden mice.
Proc. Natl. Acad. Sci. USA
98,10238
-10243.
Mayer, T. and Maltby, E. (1964). An experimental investigation of pattern development in lethal spotting and belted mouse embryos. Dev. Biol. 9, 269-286.
Mercer, J. A., Seperack, P. K., Strobel, M. C., Copeland, N. G. and Jenkins, N. A. (1991). Novel myosin heavy chain encoded by murine dilute coat colour locus. Nature 349,709 -713.[CrossRef][Medline]
Murray, J. and Snell, G. (1945). Belted, a new sixth chromosome mutation in the mouse. J. Hered. 36,266 -268.
Nusgens, B. V., Verellen-Dumoulin, C., Hermanns-Le, T., de Paepe, A., Nuytinck, L., Pierard, G. E. and Lapiere, C. M. (1992). Evidence for a relationship between Ehlers-Danlos type VII C in humans and bovine dermatosparaxis. Nat. Genet. 1,214 -217.[Medline]
Pavan, W. J. and Tilghman, S. M. (1994). Piebald lethal (sl) acts early to disrupt the development of neural crest-derived melanocytes. Proc. Natl. Acad. Sci. USA 91,7159 -7163.[Abstract]
Potterf, S. B., Furumura, M., Dunn, K. J., Arnheiter, H. and Pavan, W. J. (2000). Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3. Hum. Genet. 107,1 -6.[CrossRef][Medline]
Ross, M., LaBrie, S., McPherson, J. and Stanton, V. (1999). Screening large-insert libraries by hybridization. In Current Protocols in Human Genetics (ed. N. C. Dracopoli, J. L. Haines, B. R. Korf, D. T. Moir, C. C. Morton, C. E. Seidman, J. G. Seidman and D. R. Smith), pp. 5.6.1-5.6.52. New York, NY: John Wiley and Sons.
Schaible, R. (1972). Comparative effects of piebald-spotting genes on clones of melanocytes in different vertebrate species. In Pigmentation: Its Genesis and Biologic Control (ed. V. Riley), pp. 343-357. New York: Appleton-Century-Crofts.
Silvers, W. K. (1979). The Coat Colors of Mice. New York: Sringer-Verlag.
Somerville, R. P., Longpre, J. M., Jungers, K. A., Engle, J. M.,
Ross, M., Evanko, S., Wight, T. N., Leduc, R. and Apte, S. S.
(2003). Characterization of ADAMTS-9 and ADAMTS-20 as a distinct
ADAMTS subfamily related to Caenorhabditis elegans GON-1. J. Biol.
Chem. 278,9503
-9513.
Southard-Smith, E. M., Kos, L. and Pavan, W. J. (1998). Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Nat. Genet. 18, 60-64.[Medline]
Steel, K. P., Davidson, D. R. and Jackson, I. J.
(1992). TRP-2/DT, a new early melanoblast marker, shows that
steel growth factor (c-kit ligand) is a survival factor.
Development 115,1111
-1119.
Tortorella, M., Pratta, M., Liu, R. Q., Abbaszade, I., Ross, H.,
Burn, T. and Arner, E. (2000). The thrombospondin motif of
aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and
cleavage. J. Biol. Chem.
275,25791
-25797.
Tortorella, M. D., Burn, T. C., Pratta, M. A., Abbaszade, I.,
Hollis, J. M., Liu, R., Rosenfeld, S. A., Copeland, R. A., Decicco, C. P.,
Wynn, R. et al. (1999). Purification and cloning of
aggrecanase-1: a member of the ADAMTS family of proteins.
Science 284,1664
-1666.
Voisey, J. and van Daal, A. (2002). Agouti: from mouse to man, from skin to fat. Pigment Cell Res. 15, 10-18.[CrossRef][Medline]
Wilkinson, D. G. and Nieto, M. A. (1993). Guide to techniques in mouse development. In Methods in Enzymology (ed. P. M. Wassarman and M. L. DePamphilis), pp.361 -373. San Diego: Academic Press.
Wilson, S. M., Yip, R., Swing, D. A., O'Sullivan, T. N., Zhang,
Y., Novak, E. K., Swank, R. T., Russell, L. B., Copeland, N. G. and Jenkins,
N. A. (2000). A mutation in Rab27a causes the vesicle
transport defects observed in ashen mice. Proc. Natl. Acad. Sci.
USA 97,7933
-7938.
Wu, M., Hemesath, T. J., Takemoto, C. M., Horstmann, M. A.,
Wells, A. G., Price, E. R., Fisher, D. Z. and Fisher, D. E.
(2000). c-Kit triggers dual phosphorylations, which couple
activation and degradation of the essential melanocyte factor Mi.
Genes Dev. 14,301
-312.
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