RGD Reference Report - The mutation ROR2W749X, linked to human BDB, is a recessive mutation in the mouse, causing brachydactyly, mediating patterning of joints and modeling recessive Robinow syndrome.

General

The mutation ROR2W749X, linked to human BDB, is a recessive mutation in the mouse, causing brachydactyly, mediating patterning of joints and modeling recessive Robinow syndrome.
Authors:	Raz, R Stricker, S Gazzerro, E Clor, JL Witte, F Nistala, H Zabski, S Pereira, RC Stadmeyer, L Wang, X Gowen, L Sleeman, MW Yancopoulos, GD Canalis, E Mundlos, S Valenzuela, DM Economides, AN
Citation:	Raz R, etal., Development. 2008 May;135(9):1713-23. doi: 10.1242/dev.015149. Epub 2008 Mar 19.
RGD ID:	11535948
Pubmed:	PMID:18353862 (View Abstract at PubMed)
DOI:	DOI:10.1242/dev.015149 (Journal Full-text)
Mutations in ROR2 result in a spectrum of genetic disorders in humans that are classified, depending on the nature of the mutation and the clinical phenotype, as either autosomal dominant brachydactyly type B (BDB, MIM 113000) or recessive Robinow syndrome (RRS, MIM 268310). In an attempt to model BDB in mice, the mutation W749X was engineered into the mouse Ror2 gene. In contrast to the human situation, mice heterozygous for Ror2(W749FLAG) are normal and do not develop brachydactyly, whereas homozygous mice exhibit features resembling RRS. Furthermore, both Ror2(W749FLAG/W749FLAG) and a previously engineered mutant, Ror2(TMlacZ/TMlacZ), lack the P2/P3 joint. Absence of Gdf5 expression at the corresponding interzone suggests that the defect is in specification of the joint. As this phenotype is absent in mice lacking the entire Ror2 gene, it appears that specification of the P2/P3 joint is affected by ROR2 activity. Finally, Ror2(W749FLAG/W749FLAG) mice survive to adulthood and exhibit phenotypes (altered body composition, reduced male fertility) not observed in Ror2 knockout mice, presumably due to the perinatal lethality of the latter. Therefore, Ror2(W749FLAG/W749FLAG) mice represent a postnatal model for RRS, provide insight into the mechanism of joint specification, and uncover novel roles of Ror2 in the mouse.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
autosomal recessive Robinow syndrome		ISO	Ror2 (Mus musculus)	11535948; 11535948	DNA:nonsense mutation:cds:p.W749X(mouse)	RGD
autosomal recessive Robinow syndrome		IMP		11535948	DNA:nonsense mutation:cds:p.W749X(mouse)	RGD

Objects Annotated

Genes (Rattus norvegicus)

Ror2 (receptor tyrosine kinase-like orphan receptor 2)

Genes (Mus musculus)

Ror2 (receptor tyrosine kinase-like orphan receptor 2)

Genes (Homo sapiens)

ROR2 (receptor tyrosine kinase like orphan receptor 2)

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The mutation ROR2W749X, linked to human BDB, is a recessive mutation in the mouse, causing brachydactyly, mediating patterning of joints and modeling recessive Robinow syndrome.