Olfactomedin 2: Expression in the Eye and Interaction with Other Olfactomedin Domain–Containing Proteins

Sultana, Abeda; Nakaya, Naoki; Senatorov, Vladimir V.; Tomarev, Stanislav I.

doi:10.1167/iovs.10-6356

Cited by 13 publications

(20 citation statements)

References 43 publications

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“…In these transgenic mice, EGFP expression in the developing and adult brain coincides with known sites of Olfm1 expression, as determined by in situ hybridization (4,24). Expression of Olfm1 reaches the maximum level between the late embryonic and the early postnatal stages, as judged by in situ hybridization and quantitative PCR (25). At the embryonic stage E13, EGFP expression was detected mainly in the neuronal tissues, with the highest levels of expression in the medulla oblongata, outer area of the midbrain, DRG, and spinal cord.…”

Section: Olfm1mentioning

confidence: 76%

Olfactomedin 1 Interacts with the Nogo A Receptor Complex to Regulate Axon Growth

Nakaya

Sultana

Lee

et al. 2012

Journal of Biological Chemistry

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Section: Olfm1mentioning

confidence: 76%

Olfactomedin 1 Interacts with the Nogo A Receptor Complex to Regulate Axon Growth

Nakaya

Sultana

Lee

et al. 2012

Journal of Biological Chemistry

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“…Olfm1 and Olfm2 are able to form heterodimers and available data suggest that they may perform similar functions (Sultana et al, 2011). Shotgun analysis of proteins constituting the AMPAR complexes demonstrated that Olfm1 and Olfm2 are the components of these complexes (Schwenk et al, 2012, Shanks et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

“…GAPDH was used for normalization. Primers for Q-PCR have been previously described (Sultana et al, 2011). Each sample was analyzed in triplicates.…”

Section: Methodsmentioning

confidence: 99%

“…This antibody detected Olfm2 but not closely related Olfm1 or Olfm3 proteins expressed in HEK293 cells transiently transfected with corresponding expression constructs. A polyclonal Olfm2 peptide antibody generated against synthetic peptide RSLDARLRAADGSVSAKSF was reported previously (Sultana et al, 2011). …”

Section: Methodsmentioning

confidence: 99%

“…Olfm2, similar to Olfm1 and Olfm3, contains a signal peptide at its N-terminus and a highly conserved olfactomedin domain at its C-terminus. Our previous study has shown that Olfm2 interacts with Olfm1 and Olfm3 (Sultana et al, 2011, Nakaya et al, 2013). Moreover, mutations in any subfamily I member inhibiting its secretion also inhibit secretion of other subfamily members (Sultana et al, 2011).…”

Section: Introductionmentioning

confidence: 97%

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Deletion of olfactomedin 2 induces changes in the AMPA receptor complex and impairs visual, olfactory, and motor functions in mice

Sultana

Nakaya

Dong

et al. 2014

Experimental Neurology

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Olfactomedin 2 (Olfm2) is a secretory glycoprotein belonging to the family of olfactomedin domain-containing proteins. A previous study has shown that a mutation in OLFM2 is associated with primary open angle glaucoma in Japanese patients. In the present study, we generated Olfm2 deficient mice by replacing the Olfm2 gene with the LacZ gene. Loss of Olfm2 resulted in no gross abnormalities. However, Olfm2 null mice showed reduced exploration, locomotion, olfactory sensitivity, abnormal motor coordination, and anxiety related behavior. The pattern of the Olfm2 gene expression was studied in the brain and eye using β-galactosidase staining. In the brain, Olfm2 was mainly expressed in the olfactory bulb, cortex, piriform cortex, olfactory trabeculae, inferior and superior colliculus. In the eye expression was detected mainly in retinal ganglion cells. In Olfm2 null mice, the amplitude of the first negative wave in the visual evoked potential test was significantly reduced as compared with wild-type littermates. Olfm2, similar to Olfm1, interacted with the GluR2 subunit of the AMPAR complexes and Olfm2 co-segregated with the AMPA receptor subunit GluR2 and other synaptic proteins in the synaptosomal membrane fraction upon biochemical fractionation of adult mice cortex and retina. Immunoprecipitation from the synaptosomal membrane fraction of Olfm2 null mouse brain cortex using the GluR2 antibody showed reduced levels of several components of the AMPAR complex in the immunoprecipitates including Olfm1, PSD95 and CNIH2. These results suggest that heterodimers of Olfm1 and Olfm2 interact with AMPAR more efficiently than Olfm2 homodimers and that Olfm2 plays a role in the organization of the AMPA receptor complexes.

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Identification and functional characterisation of genetic variants in OLFM2 in children with developmental eye disorders

et al. 2016

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Anophthalmia, microphthalmia, and coloboma are a genetically heterogeneous spectrum of developmental eye disorders and affect around 30 per 100,000 live births. OLFM2 encodes a secreted glycoprotein belonging to the noelin family of olfactomedin domain-containing proteins that modulate the timing of neuronal differentiation during development. OLFM2 SNPs have been associated with open angle glaucoma in a case-control study, and knockdown of Olfm2 in zebrafish results in reduced eye size. From a cohort of 258 individuals with developmental eye anomalies, we identified two with heterozygous variants in OLFM2: an individual with bilateral microphthalmia carrying a de novo 19p13.2 microdeletion involving OLFM2 and a second individual with unilateral microphthalmia and contralateral coloboma who had a novel single base change in the 5' untranslated region. Dual luciferase assays demonstrated that the latter variant causes a significant decrease in expression of OLFM2. Furthermore, RNA in situ hybridisation experiments using human developmental tissue revealed expression in relevant structures, including the lens vesicle and optic cup. Our study indicates that OLFM2 is likely to be important in mammalian eye development and disease and should be considered as a gene for human ocular anomalies.

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Olfactomedin 2: Expression in the Eye and Interaction with Other Olfactomedin Domain–Containing Proteins

Cited by 13 publications

References 43 publications

Olfactomedin 1 Interacts with the Nogo A Receptor Complex to Regulate Axon Growth

Olfactomedin 1 Interacts with the Nogo A Receptor Complex to Regulate Axon Growth

Deletion of olfactomedin 2 induces changes in the AMPA receptor complex and impairs visual, olfactory, and motor functions in mice

Identification and functional characterisation of genetic variants in OLFM2 in children with developmental eye disorders

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