spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online August 18, 2003
doi: 10.1242/10.1242/dev.00668

This Article
Right arrow Summary Freely available
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in Development
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rao, C.
Right arrow Articles by Beier, D. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rao, C.
Right arrow Articles by Beier, D. R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

A defect in a novel ADAMTS family member is the cause of the belted white-spotting mutation

Cherie Rao1,*, Dorothee Foernzler1,*, Stacie K. Loftus2, Shanming Liu1, John D. McPherson3, Katherine A. Jungers4, Suneel S. Apte4, William J. Pavan2 and David R. Beier1,*,{dagger}

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



View larger version (122K):

[in a new window]
  		Fig. 1. Identification of a novel bt allele. The lower mouse is homozygous for btBei1. The upper mouse is derived from a cross between a homozygous btBei1 mouse and a mouse homozygous for the original bt allele, demonstrating that the two mutations fail to complement and are therefore allelic.

 


View larger version (19K):

[in a new window]
  		Fig. 2. Physical map of the bt locus. The top panel includes BAC clones obtained from a 129/Sv-genomic library. The bottom panel includes BAC clones obtained from a C57BL/6-genomic library. Black circles correspond to STSs obtained from BAC ends and used to order clones in the contig. Broken lines show the recombinant interval defined by the flanking markers 312Sp6 (an SSCP found using BAC end sequences) and D15Mit272 (an SSLP). The three BAC clones that were sequenced are shown with thick horizontal lines (RP23-24F24, Accession Number AC084384; RP23-5K17, Accession Number AC084382; RP23-54K18, Accession Number AC084385).

 


View larger version (21K):

[in a new window]
  		Fig. 3. ADAMTS20 protein structure and homologies. (A) The protein structure of the products of the short and long Adamts20 transcripts are shown. ADAMTS9 is the most closely related mammalian homolog of ADAMTS20, and GON-1 is the highly homologous C. elegans metalloprotease. (B) ClustalW analysis of the ADAMTS family. The human (h) family members are shown because these are the most well characterized. The closely related ADAMTS20 orthologs, ADAMTS9, GON-1 and the Drosophila gene GH1639p are shown in bold.

 


View larger version (51K):

[in a new window]
  		Fig. 4. Adamts20 expression during embryogenesis. Adamts20 expression was assayed by northern hybridization of polyA+ RNA at E7, E11, E15 and E17. The left panel (Adamts20-all) was analyzed using the Adex3/8 probe (see Materials and methods) that identifies both the short and long Adamts20 transcripts. The right panel (Adamts20-long) was analyzed with the TS20mid3'F/2R fragment, which identifies only the long transcript.

 


View larger version (92K):

[in a new window]
  		Fig. 5. Adamts20 expression is distinct and precedes that of melanoblast marker DCT. Adamts20 expression (B,D,F,H,J) is compared with that of melanoblast marker DCT (A,C,E,G,I) through developmental stages E9.5 (A,B), E10.5 (C,D), E11.5 (E,F), and E12.5 (G-J). Adamts20 expression in the neural tube is visible at E9.5 (B), E10.5 (D) and E11.5 (F). At E9.5, DCT is expressed only the developing pigmented retinal epithelium of the eye (A) and in migrating melanoblasts at E10.5 (C). 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 E11.5 (F) and remains expressed here through to E12.5 (H,J). This expression of Adamts20 at the base of the limb buds (black arrows in E,F) at E11.5 precedes expression of DCT detected in migrating melanoblasts in the same region, visible at E12.5 (G,I), but not at E11.5 (E). Scale bars: 1 mm in A-D; 2 mm in E-J.

 


View larger version (58K):

[in a new window]
  		Fig. 6. Adamts20 is expressed in the dermis. Radioactive in situ hybridization of Adamts20 expression during mouse skin development at E13.5 (A), E14.5 (B), E15.5 (C,D), E17.5 (E,F) and E18.5 (G,H). In A and B, the arrows indicate the epidermis where no hybridization is seen and D indicates labeling of cells in the dermis. In C,E,G, labeling of dermis is seen, as well as intense hybridization of cells in epidermal appendages. The arrows in corresponding DAPI-stained images illustrate hair follicles in D,F. (G,H) Images from the snout region showing intense staining in vibrissae follicle. Images A-C,E,G use red pseudocolor to identify silver grains viewed under dark-field illumination and blue staining corresponds to DAPI-stained nuclei viewed under UV light. Images D,F,H show DAPI staining alone of the same images shown in C,E,G, respectively. Scale bar: 50 µm.

 

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



© The Company of Biologists Ltd 2003