Ror2 knockout mouse as a model for the developmental pathology of autosomal recessive Robinow syndrome

被引：100
作者：
Schwabe, GC
Trepczik, B
Süring, K
Brieske, N
Tucker, AS
Sharpe, PT
Minami, Y
Mundlos, S
机构：
[1] Max Planck Inst Mol Genet, D-14195 Berlin, Germany
[2] Humboldt Univ, Charite, Inst Med Genet, Berlin, Germany
[3] Humboldt Univ, Charite, Dept Trauma & Reconstruct Surg, Berlin, Germany
[4] Univ London Kings Coll, Guys Hosp, GKT Dent Inst, Dept Craniofacial Dev, London WC2R 2LS, England
[5] Kobe Univ, Grad Sch Med, Dept Genome Sci, Kobe, Hyogo, Japan
来源：
DEVELOPMENTAL DYNAMICS | 2004年 / 229卷 / 02期
关键词：
Ror2; Robinow syndrome; somitogenesis; development of limb; craniofacies; genital;
D O I：
10.1002/dvdy.10466
中图分类号：
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号：
100101 ;
摘要：
Robinow syndrome (RS) is a human dwarfism syndrome characterized by mesomelic limb shortening, vertebral and craniofacial malformations and small external genitals. We have analyzed Ror2(-/-) mice as a model for the developmental pathology of RS. Our results demonstrate that vertebral malformations in Ror2(-/-) mice are due to reductions in the presomitic mesoderm and defects in somitogenesis. Mesomelic limb shortening in Ror2(-/-) mice is a consequence of perturbed chondrocyte differentiation. Moreover, we show that the craniofacial phenotype is caused by a midline outgrowth defect. Ror2 expression in the genital tubercle and its reduced size in Ror2(-/-) mice makes it likely that Ror2 is involved in genital development. In conclusion, our findings suggest that Ror2 is essential at multiple sites during development. The Ror2(-/-) mouse provides a suitable model that may help to explain many of the underlying developmental malformations in individuals with Robinow syndrome.
引用
收藏
页码：400 / 410
页数：11
相关论文
共 64 条
[1]   Recessive Robinow syndrome, allelic to dominant brachydactyly type B, is caused by mutation of ROR2 [J].
Afzal, AR ;
Rajab, A ;
Fenske, CD ;
Oldridge, M ;
Elanko, N ;
Ternes-Pereira, E ;
Tüysüz, B ;
Murday, VA ;
Patton, MA ;
Wilkie, AOM ;
Jeffery, S .
NATURE GENETICS, 2000, 25 (04) :419-422
[2]   Expression of the Ror1 and Ror2 receptor tyrosine kinase genes during mouse development [J].
Al-Shawi, R ;
Ashton, SV ;
Underwood, C ;
Simons, JP .
DEVELOPMENT GENES AND EVOLUTION, 2001, 211 (04) :161-171
[3]   The synpolydactyly homolog (spdh) mutation in the mouse -: a defect in patterning and growth of limb cartilage elements [J].
Albrecht, AN ;
Schwabe, GC ;
Stricker, S ;
Böddrich, A ;
Wanker, EE ;
Mundlos, S .
MECHANISMS OF DEVELOPMENT, 2002, 112 (1-2) :53-67
[4]   Wnt3A plays a major role in the segmentation clock controlling somitogenesis [J].
Aulehla, A ;
Wehrle, C ;
Brand-Saberi, B ;
Kemler, R ;
Gossler, A ;
Kanzler, B ;
Herrmann, BG .
DEVELOPMENTAL CELL, 2003, 4 (03) :395-406
[5]  
Belo JA, 2000, GENESIS, V26, P265, DOI 10.1002/(SICI)1526-968X(200004)26:4<265::AID-GENE80>3.3.CO
[6]  
2-W
[7]   Murine cerberus homologue mCer-1: A candidate anterior patterning molecule [J].
Biben, C ;
Stanley, E ;
Fabri, L ;
Kotecha, S ;
Rhinn, M ;
Drinkwater, C ;
Lah, M ;
Wang, CC ;
Nash, A ;
Hilton, D ;
Ang, SL ;
Mohun, T ;
Harvey, RP .
DEVELOPMENTAL BIOLOGY, 1998, 194 (02) :135-151
[8]   HEDGEHOG AND BMP GENES ARE COEXPRESSED AT MANY DIVERSE SITES OF CELL-CELL INTERACTION IN THE MOUSE EMBRYO [J].
BITGOOD, MJ ;
MCMAHON, AP .
DEVELOPMENTAL BIOLOGY, 1995, 172 (01) :126-138
[9]   Requirement of the paraxis gene for somite formation and musculoskeletal patterning [J].
Burgess, R ;
Rawls, A ;
Brown, D ;
Bradley, A ;
Olson, EN .
NATURE, 1996, 384 (6609) :570-573
[10]   PARAXIS - A BASIC HELIX-LOOP-HELIX PROTEIN EXPRESSED IN PARAXIAL MESODERM AND DEVELOPING SOMITES [J].
BURGESS, R ;
CSERJESI, P ;
LIGON, KL ;
OLSON, EN .
DEVELOPMENTAL BIOLOGY, 1995, 168 (02) :296-306
1234567