Ror1 is one of the two vertebrate Ror-family members of orphan receptor-tyrosine kinases (Yoda et al.,2003; Green et al.,2008; Minami et al.,2009). Like its closely related family member Ror2, Ror1 contains an extracellular cysteine-rich domain (CRD) similar to the CRD domain of the Wnt-receptor frizzled (Saldanha et al.,1998). It has been demonstrated that Ror2 can bind to Wnt-ligands as well as to the BMP/TGFβ-family member, Gdf5 (Oishi et al.,2003; Sammar et al.,2004; Liu et al.,2008). Ror2 activity can mediate non-canonical Wnt-signaling through interaction with Wnt5a, and modulates the canonical Wnt-signaling pathway through differential interaction with the Frizzled receptor (Hikasa et al.,2002; Mikels and Nusse,2006; He et al.,2008; Li et al.,2008). Ror1 has been recently demonstrated to be capable of binding the Wnt5a ligand as well. However, whether this binding results in functional activity is currently not known (Fukuda et al.,2008). Both Ror genes are widely expressed during embryonic development, in limbs, perichondrium of the developing long bones, teeth, heart, lung, liver, gut, urogenital tract, and hippocampal neurons (Oishi et al.,1999; Al-Shawi et al.,2001; Matsuda et al.,2001; Paganoni and Ferreira,2003; Rodriguez-Niedenfuhr et al.,2004; Schwabe et al.,2004). Mutations in ROR2 in humans cause autosomal dominant brachydactyly type B (BDB) and are associated with an autosomal recessive form of Robinow syndrome (RS) (Afzal et al.,2000; Oldridge et al.,2000; Schwabe et al.,2000; van Bokhoven et al.,2000; Hamamy et al.,2006). Loss of Ror2 in mice results in phenotypic changes resembling RS (DeChiara et al.,2000; Takeuchi et al.,2000; Schwabe et al.,2004). The point mutation Ror2-W749X, linked to human BDB, behaves as a recessive mutation in mouse causing brachydactyly and models recessive RS (Raz et al.,2008). In addition, ROR family member have been implicated in tumor formation in humans. ROR1 has been found to be overexpressed in patients with acute and chronic lymphoblastic leukemia (Shabani et al.,2007,2008; Daneshmanesh et al.,2008) and was found to act as a survival kinase in HeLa cervical carcinoma cells (MacKeigan et al.,2005). ROR2 has been found to be overexpressed in squamous cell carcinoma, renal cell carcinoma, and metastatic melanoma, and to regulate osteosarcoma cell invasiveness (Enomoto et al.,2009; Kobayashi et al.,2009; Morioka et al.,2009; Wright et al.,2009; O'Connell et al.,2010). Previously it was reported that loss of Ror1 in mice results in perinatal lethality due to respiratory defects, but that these mice lack any abnormalities in skeletogenesis (Nomi et al.,2001). Here, we have re-examined the Ror1 mutants and found that the mice have subtle skeletal defects at birth; they showed fusions of the sternebrae, a cleft in the basisphenoid bone, and abnormal development of the cervical vertebral element C2. Homozygous mice survived in our facility and displayed abnormal synchondrosis in the cranial base, postnatal growth retardation, and age-related skeletal changes. Furthermore, we observed additional phenotypic defects in Ror1−/− mutants, such as female infertility probably due to an imperforated hymen, kidney defects, and occasionally enlarged seminal vesicles in Ror1−/− males.