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Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice.

Mizuhashi K, Chaya T, Kanamoto T, Omori Y, Furukawa T - PLoS ONE (2015)

Bottom Line: First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain.Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated.These findings suggest that Obif plays essential roles in the development of multiple tissues.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, Japan; Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka, Japan.

ABSTRACT

Background: Various kinds of transmembrane and secreted proteins play pivotal roles in development through cell-cell communication. We previously reported that Obif (Osteoblast induction factor, Tmem119), encoding a single transmembrane protein, is expressed in differentiating osteoblasts, and that Obif-/- mice exhibit significantly reduced bone volume in the femur. In the current study, we characterized the Obif protein and further investigated the biological phenotypes of a variety of tissues in Obif-/- mice.

Results: First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain. Next, we observed that Obif-/- mice exhibit bone dysplasia in association with significantly increased osteoid volume per osteoid surface (OV/OS) and osteoid maturation time (Omt), and significantly decreased mineral apposition rate (MAR) and bone formation rate per bone surface (BFR/BS). In addition, we observed that Obif-/- mice show a significant decrease in testis weight as well as in sperm number. By histological analysis, we found that Obif is expressed in spermatocytes and spermatids in the developing testis and that spermatogenesis is halted at the round spermatid stage in the Obif-/- testis that lacks sperm. However, the number of litters fathered by male mice was slightly reduced in Obif-/- mice compared with wild-type mice, although this was not statistically significant.

Conclusions: Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated. In addition, we found that Obif is required for normal bone mineralization and late testicular differentiation in vivo. These findings suggest that Obif plays essential roles in the development of multiple tissues.

No MeSH data available.


Related in: MedlinePlus

Loss of Obif impaired bone growth.(A) CR lengths from wild-type (white box) and Obif−/− mice (black box) at 8 wks. (B) Longitudinal bone lengths of radius, humerus, tibia, and femur in wild-type (white box) and Obif−/− mice (black box) at 8 wks. CR length, crown-rump length. Error bars show the SEM (n = 5). *P < 0.05.
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pone.0133704.g002: Loss of Obif impaired bone growth.(A) CR lengths from wild-type (white box) and Obif−/− mice (black box) at 8 wks. (B) Longitudinal bone lengths of radius, humerus, tibia, and femur in wild-type (white box) and Obif−/− mice (black box) at 8 wks. CR length, crown-rump length. Error bars show the SEM (n = 5). *P < 0.05.

Mentions: To investigate bone development in Obif−/− mice more extensively, we measured longitudinal bone lengths of the radius, humerus, tibia, and femur at 8 wks (Fig 2). We compared the bone length of the radius, humerus, tibia, and femur, which represent endochondral ossification, between wild-type and Obif−/− mice (Fig 2). All of the bone lengths of the radius, humerus, tibia, and femur in Obif−/− mice were significantly shorter than those in wild-type mice. These data suggest that bone development is widely impaired in Obif−/− mice.


Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice.

Mizuhashi K, Chaya T, Kanamoto T, Omori Y, Furukawa T - PLoS ONE (2015)

Loss of Obif impaired bone growth.(A) CR lengths from wild-type (white box) and Obif−/− mice (black box) at 8 wks. (B) Longitudinal bone lengths of radius, humerus, tibia, and femur in wild-type (white box) and Obif−/− mice (black box) at 8 wks. CR length, crown-rump length. Error bars show the SEM (n = 5). *P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4514473&req=5

pone.0133704.g002: Loss of Obif impaired bone growth.(A) CR lengths from wild-type (white box) and Obif−/− mice (black box) at 8 wks. (B) Longitudinal bone lengths of radius, humerus, tibia, and femur in wild-type (white box) and Obif−/− mice (black box) at 8 wks. CR length, crown-rump length. Error bars show the SEM (n = 5). *P < 0.05.
Mentions: To investigate bone development in Obif−/− mice more extensively, we measured longitudinal bone lengths of the radius, humerus, tibia, and femur at 8 wks (Fig 2). We compared the bone length of the radius, humerus, tibia, and femur, which represent endochondral ossification, between wild-type and Obif−/− mice (Fig 2). All of the bone lengths of the radius, humerus, tibia, and femur in Obif−/− mice were significantly shorter than those in wild-type mice. These data suggest that bone development is widely impaired in Obif−/− mice.

Bottom Line: First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain.Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated.These findings suggest that Obif plays essential roles in the development of multiple tissues.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, Japan; Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka, Japan.

ABSTRACT

Background: Various kinds of transmembrane and secreted proteins play pivotal roles in development through cell-cell communication. We previously reported that Obif (Osteoblast induction factor, Tmem119), encoding a single transmembrane protein, is expressed in differentiating osteoblasts, and that Obif-/- mice exhibit significantly reduced bone volume in the femur. In the current study, we characterized the Obif protein and further investigated the biological phenotypes of a variety of tissues in Obif-/- mice.

Results: First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain. Next, we observed that Obif-/- mice exhibit bone dysplasia in association with significantly increased osteoid volume per osteoid surface (OV/OS) and osteoid maturation time (Omt), and significantly decreased mineral apposition rate (MAR) and bone formation rate per bone surface (BFR/BS). In addition, we observed that Obif-/- mice show a significant decrease in testis weight as well as in sperm number. By histological analysis, we found that Obif is expressed in spermatocytes and spermatids in the developing testis and that spermatogenesis is halted at the round spermatid stage in the Obif-/- testis that lacks sperm. However, the number of litters fathered by male mice was slightly reduced in Obif-/- mice compared with wild-type mice, although this was not statistically significant.

Conclusions: Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated. In addition, we found that Obif is required for normal bone mineralization and late testicular differentiation in vivo. These findings suggest that Obif plays essential roles in the development of multiple tissues.

No MeSH data available.


Related in: MedlinePlus