Ror2, encoding a receptor-like tyrosine kinase, is required for cartilage and growth plate development

DeChiara, Thomas M.; Kimble, Robert B.; Poueymirou, William; Rojas, José Luis Vázquez; Masiakowski, Piotr; Valenzuela, David M.; Yancopouloš, George D.

doi:10.1038/73488

Cited by 223 publications

(175 citation statements)

References 28 publications

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“…The protein encoded by ROR2 is a type I transmembrane protein and may be involved in the early formation of chondrocytes 25 . GLB1 encodes beta-galactosidase-1, a lysosomal hydrolase, and a variant within this gene causes GM1-gangliosidosis.…”

Section: Discussionmentioning

confidence: 99%

ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention

et al. 2008

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Background-Use of drug-eluting stents (DES) has reduced in-stent restenosis after percutaneous coronary intervention (PCI); however, DES are associated with late stent thrombosis. There is no accurate way to predict in-stent restenosis, although risk factors for atherosclerosis overlap those for in-stent restenosis. Therefore, we evaluated atherosclerosis candidate genes for association with in-stent restenosis.

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Section: Discussionmentioning

confidence: 99%

ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention

et al. 2008

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“…Unlike Ror2 knockout mice (Takeuchi et al, 2000;DeChiara et al, 2000), Ror2 W749FLAG/W749FLAG animals are viable, allowing the study of the effect of this ROR2 truncation postnatally. This animal model exhibits many of the features of RRS, and uncovers novel phenotypes in fertility and body composition.…”

Section: W749xmentioning

confidence: 99%

The mutationROR2W749X, linked to human BDB, is a recessive mutation in the mouse, causing brachydactyly, mediating patterning of joints and modeling recessive Robinow syndrome

et al. 2008

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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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“…Given the overall phenotypic similarity between two Ror2 alleles (DeChiara et al, 2000;Takeuchi et al, 2000;Laird et al, 2011), we analyzed ovaries from knockouts. Ror2 −/− ovaries were also smaller than WT controls and the number of germ cells was decreased ( Fig.…”

Section: Meiotic Initiation Is Independent Of Germ Cell Numbermentioning

confidence: 99%

Meiotic onset is reliant on spatial distribution but independent of germ cell number in the mouse ovary

Arora

Ross

Cantu

et al. 2016

Journal of Cell Science

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Mouse ovarian germ cells enter meiosis in a wave that propagates from anterior to posterior, but little is known about contribution of germ cells to initiation or propagation of meiosis. In a Ror2 mutant with diminished germ cell number and migration, we find that overall timing of meiotic initiation is delayed at the population level. We use chemotherapeutic depletion to exclude a profoundly reduced number of germ cells as a cause for meiotic delay. We rule out sex reversal or failure to specify somatic support cells as contributors to the meiotic phenotype. Instead, we find that anomalies in the distribution of germ cells as well as gonad shape in mutants contribute to aberrant initiation of meiosis. Our analysis supports a model of meiotic initiation via diffusible signal(s), excludes a role for germ cells in commencing the meiotic wave and furnishes the first phenotypic demonstration of the wave of meiotic entry. Finally, our studies underscore the importance of considering germ cell migration defects while studying meiosis to discern secondary effects resulting from positioning versus primary meiotic entry phenotypes.

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Ror2, encoding a receptor-like tyrosine kinase, is required for cartilage and growth plate development

Cited by 223 publications

References 28 publications

ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention

ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention

The mutationROR2W749X, linked to human BDB, is a recessive mutation in the mouse, causing brachydactyly, mediating patterning of joints and modeling recessive Robinow syndrome

Meiotic onset is reliant on spatial distribution but independent of germ cell number in the mouse ovary

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