The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Lois J Arend - One of the best experts on this subject based on the ideXlab platform.
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Novel roles of Pkd2 in male reproductive system development.
Differentiation; research in biological diversity, 2014Co-Authors: Xuguang Nie, Lois J ArendAbstract:Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited genetic diseases, caused by mutations in PKD1 and/ or PKD2. Infertility and reproductive tract abnormalities in male ADPKD patients are very common and have higher incidence than in the general population. In this work, we reveal novel roles of Pkd2 for male reproductive system development. Disruption of Pkd2 caused dilation of Mesonephric Tubules/efferent ducts, failure of epididymal coiling, and defective testicular development. Deletion of Pkd2 in the epithelia alone was sufficient to cause reproductive tract defects seen in Pkd2(-/-) mice, suggesting that epithelial Pkd2 plays a pivotal role for development and maintenance of the male reproductive tract. In the testis, Pkd2 also plays a role in interstitial tissue and testicular cord development. In-depth analysis of epithelial-specific knockout mice revealed that Pkd2 is critical to maintain cellular phenotype and developmental signaling in the male reproductive system. Taken together, our data for the first time reveal novel roles for Pkd2 in male reproductive system development and provide new insights in male reproductive system abnormality and infertility in ADPKD patients.
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Pkd1 is required for male reproductive tract development
Mechanisms of Development, 2013Co-Authors: Xuguang Nie, Lois J ArendAbstract:Reproductive tract abnormalities and male infertility have higher incidence in ADPKD patients than in general populations. In this work, we reveal that Pkd1, whose mutations account for 85% of ADPKD cases, is essential for male reproductive tract development. Disruption of Pkd1 caused multiple organ defects in the murine male reproductive tract. The earliest visible defect in the Pkd1(-/-) reproductive tract was cystic dilation of the efferent ducts, which are derivatives of the Mesonephric Tubules. Epididymis development was delayed or arrested in the Pkd1(-/-) mice. No sign of epithelial coiling was seen in the null mutants. Disruption of Pkd1 in epithelium alone using the Pax2-cre mice was sufficient to cause efferent duct dilation and coiling defect in the epididymis, suggesting that Pkd1 is critical for epithelium development and maintenance in male reproductive tract. In-depth analysis showed that Pkd1 is required to maintain tubulin cytoskeleton and important for Tgf-β/Bmp signal transduction in epithelium of male reproductive tract. Altogether, our results for the first time provide direct evidence for developmental roles of Pkd1 in the male reproductive tract and provide new insights in reproductive tract abnormalities and infertility in ADPKD patients.
Yasuhiro Kon - One of the best experts on this subject based on the ideXlab platform.
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Ovarian cysts in MRL / MpJ mice are derived from the extraovarian rete: a developmental study.
Journal of anatomy, 2011Co-Authors: Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yuka Namiki, Elewa Yaser Hosney, Yasuhiro KonAbstract:MRL/MpJ (MRL) mice, commonly used as a model for autoimmune disease, have a high frequency of ovarian cysts originating from the rete ovarii. In the present study, to clarify how the rete ovarii, which are remnants of Mesonephric Tubules during embryogenesis, progress to cystic formation with aging, the morphology of MRL rete ovarii was analyzed and compared with that of normal C57BL/6N (B6) mice. In B6 mice, the rete ovarii consisted of a series of Tubules, including the extraovarian rete (ER), the connecting rete (CR), and the intraovarian rete (IR), based on their location. Whereas the ER of B6 mice was composed of highly convoluted Tubules lined by both ciliated and non-ciliated epithelia, the Tubules in the CR and IR had only non-ciliated cells. In MRL mice, dilations of the rete ovarii initiated from the IR rather than the ER or CR. Although the histological types of cells lining the lumen of the rete ovarii were the same as those in B6 mice, the ER in MRL mice showed a variety in morphology. In particular, the connections between the ER and ovary tended to disappear with increasing age and the development of ovarian cysts. Furthermore, the epithelium lining the large ovarian cysts in MRL mice had ciliated cells forming the cluster. On the basis of these findings, it is suggested that cystic changes of the rete ovarii in MRL mice are caused by the dilations of the IR with invasion of the ER and CR into the ovarian medulla. These data provide new pathological mechanisms for ovarian cyst formation.
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Identifying a new locus that regulates the development of rete ovarian cysts in MRL/MpJ mice.
The Japanese journal of veterinary research, 2011Co-Authors: Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yuka Namiki, Yasuhiro KonAbstract:MRL/MpJ (MRL) is a mouse model for autoimmune disease and develops ovarian cysts with age. The ovarian cysts originate from the rete ovarii, which is considered to be the remnant of fetal Mesonephric Tubules. In a previous study, we analyzed the genetic background of ovarian cysts by using backcross progenies between MRL and C57BL/6N (B6) mice. By interval mapping, suggestive linkages were detected on several chromosomes (Chrs), and a significant linkage on Chr 14 was designated as MRL Rete Ovarian Cyst (mroc). In the present study, which evaluated 113 F2 intercross progenies, a significant linkage appeared on Chr 6 at the marker position D6Mit188 (likelihood ratio statistic = 18.5). In particular, the peak regions of Chrs 6 and 14, which contain major causative loci by backcross analysis, showed close reverse interaction. From these results, a locus on Chr 6 was identified as mroc2, the second major locus associated with ovarian cyst formation in MRL mice.
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Quantitative trait locus analysis of ovarian cysts derived from rete ovarii in MRL/MpJ mice
Mammalian Genome, 2010Co-Authors: Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro KonAbstract:MRL/MpJ (MRL) is a model mouse for autoimmune diseases such as dermatitis, vasculitis, arthritis, and glomerulonephritis. In addition to these immune-associated disorders, we found that older MRL mice develop ovarian cysts originating from the rete ovarii, which is lined by ciliated or nonciliated epithelium and considered remnants of Mesonephric Tubules. Ovarian cysts, which are reported to have several sources, are associated with female infertility, but information regarding the genetic etiology of ovarian cysts originating from the rete ovarii is rare. In this study, to elucidate the genetic background of development of ovarian cysts, we performed quantitative trait locus (QTL) analysis using 120 microsatellite markers, which cover the whole genome of murine chromosomes, and 213 backcross progenies between female MRL and male C57BL/6N mice. The quantitative trait measured was the circumferences of rete ovarii or ovarian cysts. As a result, suggestive linkages were detected on Chrs 3, 4, 6, and 11, but significant linkages were located on Chr 14 by interval mapping. We thereby designated the 27.5-cM region of Chr 14 “MRL Rete Ovarian Cysts ( mroc ).” The peak regions of Chrs 4 and 14 in particular showed a close additive interaction ( p
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Quantitative trait locus analysis of ovarian cysts derived from rete ovarii in MRL/MpJ mice.
Mammalian genome : official journal of the International Mammalian Genome Society, 2010Co-Authors: Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro KonAbstract:MRL/MpJ (MRL) is a model mouse for autoimmune diseases such as dermatitis, vasculitis, arthritis, and glomerulonephritis. In addition to these immune-associated disorders, we found that older MRL mice develop ovarian cysts originating from the rete ovarii, which is lined by ciliated or nonciliated epithelium and considered remnants of Mesonephric Tubules. Ovarian cysts, which are reported to have several sources, are associated with female infertility, but information regarding the genetic etiology of ovarian cysts originating from the rete ovarii is rare. In this study, to elucidate the genetic background of development of ovarian cysts, we performed quantitative trait locus (QTL) analysis using 120 microsatellite markers, which cover the whole genome of murine chromosomes, and 213 backcross progenies between female MRL and male C57BL/6N mice. The quantitative trait measured was the circumferences of rete ovarii or ovarian cysts. As a result, suggestive linkages were detected on Chrs 3, 4, 6, and 11, but significant linkages were located on Chr 14 by interval mapping. We thereby designated the 27.5-cM region of Chr 14 "MRL Rete Ovarian Cysts (mroc)." The peak regions of Chrs 4 and 14 in particular showed a close additive interaction (p < 0.00001). From these results we concluded that multiple loci on Chrs 3, 4, 6, 11, and 14 interact to result in development of ovarian cysts in MRL mice.
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Cellular distribution of napsin (kidney-derived aspartic protease-like protein, KAP) mRNA in the kidney, lung and lymphatic organs of adult and developing mice.
Archives of histology and cytology, 2001Co-Authors: Koshi Mori, Yasuhiro Kon, Akihiro Konno, Toshihiko IwanagaAbstract:Kidney-derived aspartic protease-like protein (KAP), initially identified in the mouse kidney, is a novel aspartic protease exclusively expressed in the lung and spleen as well as the kidney. Its orthologues have been identified in the human and rat, and termed napsin. We performed in situ hybridization analysis to determine the cellular expression of napsin mRNA in the kidney, Iung, and lymphatic organs of adult mice and to demonstrate, for the first time, its expression patterns in ontogeny. In the adult mouse kidney, extremely intense signals for napsin mRNA were observed in the proximal straight and convoluted Tubules, in agreement with a previous study. The first signals for napsin mRNA during nephrogenesis occurred selectively in Mesonephric Tubules at embryonic day 13, and in metanephric Tubules from embryonic day 14. In the lung, a distribution restricted to type II alveolar cells or their precursors was found from embryonic day 15, at the onset of type II cell differentiation, to the adult stage. In the spleen, the mRNA was expressed in lymph nodules of the white pulp and the marginal zone - namely. B-lymphocyte-rich regions - from postnatal day 0 to adult. The lymph node and Peyer’s patch displayed similar expression patterns, but T cell-dependent areas in these organs and the thymus lacked such signals. These findings suggest that mouse napsin possesses crucial functional roles not only in the kidney but also in the lung and lymphatic tissues, even during fetal stages.
Yamada - One of the best experts on this subject based on the ideXlab platform.
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Midline-derived Shh regulates Mesonephric tubule formation through the paraxial mesoderm ☆
Developmental biology, 2013Co-Authors: Aki Murashima, Hiroki Akita, Mika Okazawa, Satoshi Kishigami, Naomi Nakagata, Ryuichi Nishinakamura, YamadaAbstract:During organogenesis, Sonic hedgehog (Shh) possesses dual functions: Shh emanating from midline structures regulates the positioning of bilateral structures at early stages, whereas organ-specific Shh locally regulates organ morphogenesis at later stages. The mesonephros is a transient embryonic kidney in amniote, whereas it becomes definitive adult kidney in some anamniotes. Thus, elucidating the regulation of mesonephros formation has important implications for our understanding of kidney development and evolution. In Shh knockout (KO) mutant mice, the mesonephros was displaced towards the midline and ectopic Mesonephric Tubules (MTs) were present in the caudal mesonephros. Mesonephros-specific ablation of Shh in Hoxb7-Cre;Shhflox/− and Sall1CreERT2/+;Shhflox/− mice embryos indicated that Shh expressed in the mesonephros was not required for either the development of the mesonephros or the differentiation of the male reproductive tract. Moreover, stage-specific ablation of Shh in ShhCreERT2/flox mice showed that notochord- and/or floor plate-derived Shh were essential for the regulation of the number and position of MTs. Lineage analysis of hedgehog (Hh)-responsive cells, and analysis of gene expression in Shh KO embryos suggested that Shh regulated nephrogenic gene expression indirectly, possibly through effects on the paraxial mesoderm. These data demonstrate the essential role of midline-derived Shh in local tissue morphogenesis and differentiation.
Xuguang Nie - One of the best experts on this subject based on the ideXlab platform.
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Novel roles of Pkd2 in male reproductive system development.
Differentiation; research in biological diversity, 2014Co-Authors: Xuguang Nie, Lois J ArendAbstract:Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited genetic diseases, caused by mutations in PKD1 and/ or PKD2. Infertility and reproductive tract abnormalities in male ADPKD patients are very common and have higher incidence than in the general population. In this work, we reveal novel roles of Pkd2 for male reproductive system development. Disruption of Pkd2 caused dilation of Mesonephric Tubules/efferent ducts, failure of epididymal coiling, and defective testicular development. Deletion of Pkd2 in the epithelia alone was sufficient to cause reproductive tract defects seen in Pkd2(-/-) mice, suggesting that epithelial Pkd2 plays a pivotal role for development and maintenance of the male reproductive tract. In the testis, Pkd2 also plays a role in interstitial tissue and testicular cord development. In-depth analysis of epithelial-specific knockout mice revealed that Pkd2 is critical to maintain cellular phenotype and developmental signaling in the male reproductive system. Taken together, our data for the first time reveal novel roles for Pkd2 in male reproductive system development and provide new insights in male reproductive system abnormality and infertility in ADPKD patients.
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Pkd1 is required for male reproductive tract development
Mechanisms of Development, 2013Co-Authors: Xuguang Nie, Lois J ArendAbstract:Reproductive tract abnormalities and male infertility have higher incidence in ADPKD patients than in general populations. In this work, we reveal that Pkd1, whose mutations account for 85% of ADPKD cases, is essential for male reproductive tract development. Disruption of Pkd1 caused multiple organ defects in the murine male reproductive tract. The earliest visible defect in the Pkd1(-/-) reproductive tract was cystic dilation of the efferent ducts, which are derivatives of the Mesonephric Tubules. Epididymis development was delayed or arrested in the Pkd1(-/-) mice. No sign of epithelial coiling was seen in the null mutants. Disruption of Pkd1 in epithelium alone using the Pax2-cre mice was sufficient to cause efferent duct dilation and coiling defect in the epididymis, suggesting that Pkd1 is critical for epithelium development and maintenance in male reproductive tract. In-depth analysis showed that Pkd1 is required to maintain tubulin cytoskeleton and important for Tgf-β/Bmp signal transduction in epithelium of male reproductive tract. Altogether, our results for the first time provide direct evidence for developmental roles of Pkd1 in the male reproductive tract and provide new insights in reproductive tract abnormalities and infertility in ADPKD patients.
Shin-hyo Lee - One of the best experts on this subject based on the ideXlab platform.
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Ovarian cysts in MRL / MpJ mice are derived from the extraovarian rete: a developmental study.
Journal of anatomy, 2011Co-Authors: Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yuka Namiki, Elewa Yaser Hosney, Yasuhiro KonAbstract:MRL/MpJ (MRL) mice, commonly used as a model for autoimmune disease, have a high frequency of ovarian cysts originating from the rete ovarii. In the present study, to clarify how the rete ovarii, which are remnants of Mesonephric Tubules during embryogenesis, progress to cystic formation with aging, the morphology of MRL rete ovarii was analyzed and compared with that of normal C57BL/6N (B6) mice. In B6 mice, the rete ovarii consisted of a series of Tubules, including the extraovarian rete (ER), the connecting rete (CR), and the intraovarian rete (IR), based on their location. Whereas the ER of B6 mice was composed of highly convoluted Tubules lined by both ciliated and non-ciliated epithelia, the Tubules in the CR and IR had only non-ciliated cells. In MRL mice, dilations of the rete ovarii initiated from the IR rather than the ER or CR. Although the histological types of cells lining the lumen of the rete ovarii were the same as those in B6 mice, the ER in MRL mice showed a variety in morphology. In particular, the connections between the ER and ovary tended to disappear with increasing age and the development of ovarian cysts. Furthermore, the epithelium lining the large ovarian cysts in MRL mice had ciliated cells forming the cluster. On the basis of these findings, it is suggested that cystic changes of the rete ovarii in MRL mice are caused by the dilations of the IR with invasion of the ER and CR into the ovarian medulla. These data provide new pathological mechanisms for ovarian cyst formation.
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Identifying a new locus that regulates the development of rete ovarian cysts in MRL/MpJ mice.
The Japanese journal of veterinary research, 2011Co-Authors: Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yuka Namiki, Yasuhiro KonAbstract:MRL/MpJ (MRL) is a mouse model for autoimmune disease and develops ovarian cysts with age. The ovarian cysts originate from the rete ovarii, which is considered to be the remnant of fetal Mesonephric Tubules. In a previous study, we analyzed the genetic background of ovarian cysts by using backcross progenies between MRL and C57BL/6N (B6) mice. By interval mapping, suggestive linkages were detected on several chromosomes (Chrs), and a significant linkage on Chr 14 was designated as MRL Rete Ovarian Cyst (mroc). In the present study, which evaluated 113 F2 intercross progenies, a significant linkage appeared on Chr 6 at the marker position D6Mit188 (likelihood ratio statistic = 18.5). In particular, the peak regions of Chrs 6 and 14, which contain major causative loci by backcross analysis, showed close reverse interaction. From these results, a locus on Chr 6 was identified as mroc2, the second major locus associated with ovarian cyst formation in MRL mice.
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Quantitative trait locus analysis of ovarian cysts derived from rete ovarii in MRL/MpJ mice
Mammalian Genome, 2010Co-Authors: Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro KonAbstract:MRL/MpJ (MRL) is a model mouse for autoimmune diseases such as dermatitis, vasculitis, arthritis, and glomerulonephritis. In addition to these immune-associated disorders, we found that older MRL mice develop ovarian cysts originating from the rete ovarii, which is lined by ciliated or nonciliated epithelium and considered remnants of Mesonephric Tubules. Ovarian cysts, which are reported to have several sources, are associated with female infertility, but information regarding the genetic etiology of ovarian cysts originating from the rete ovarii is rare. In this study, to elucidate the genetic background of development of ovarian cysts, we performed quantitative trait locus (QTL) analysis using 120 microsatellite markers, which cover the whole genome of murine chromosomes, and 213 backcross progenies between female MRL and male C57BL/6N mice. The quantitative trait measured was the circumferences of rete ovarii or ovarian cysts. As a result, suggestive linkages were detected on Chrs 3, 4, 6, and 11, but significant linkages were located on Chr 14 by interval mapping. We thereby designated the 27.5-cM region of Chr 14 “MRL Rete Ovarian Cysts ( mroc ).” The peak regions of Chrs 4 and 14 in particular showed a close additive interaction ( p
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Quantitative trait locus analysis of ovarian cysts derived from rete ovarii in MRL/MpJ mice.
Mammalian genome : official journal of the International Mammalian Genome Society, 2010Co-Authors: Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro KonAbstract:MRL/MpJ (MRL) is a model mouse for autoimmune diseases such as dermatitis, vasculitis, arthritis, and glomerulonephritis. In addition to these immune-associated disorders, we found that older MRL mice develop ovarian cysts originating from the rete ovarii, which is lined by ciliated or nonciliated epithelium and considered remnants of Mesonephric Tubules. Ovarian cysts, which are reported to have several sources, are associated with female infertility, but information regarding the genetic etiology of ovarian cysts originating from the rete ovarii is rare. In this study, to elucidate the genetic background of development of ovarian cysts, we performed quantitative trait locus (QTL) analysis using 120 microsatellite markers, which cover the whole genome of murine chromosomes, and 213 backcross progenies between female MRL and male C57BL/6N mice. The quantitative trait measured was the circumferences of rete ovarii or ovarian cysts. As a result, suggestive linkages were detected on Chrs 3, 4, 6, and 11, but significant linkages were located on Chr 14 by interval mapping. We thereby designated the 27.5-cM region of Chr 14 "MRL Rete Ovarian Cysts (mroc)." The peak regions of Chrs 4 and 14 in particular showed a close additive interaction (p < 0.00001). From these results we concluded that multiple loci on Chrs 3, 4, 6, 11, and 14 interact to result in development of ovarian cysts in MRL mice.