Generation of a new mouse line with conditionally activated signaling through the BMP receptor, ACVR1: A tool to characterize pleiotropic roles of BMP functions
Summary BMP signaling plays pleiotropic roles in various tissues during embryogenesis and after birth. We have previously generated a constitutively activated Acvr1(ca‐Acvr1) transgenic mouse line (line L35) through pronuclei injection to investigate impacts of enhanced BMP signaling in a tissue spe...
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creator | Yang, Jingwen Toda Nakamura, Masako Hallett, Shawn A. Ueharu, Hiroki Zhang, Honghao Kelley, Kristen Fukuda, Tomokazu Komatsu, Yoshihiro Mishina, Yuji |
description | Summary
BMP signaling plays pleiotropic roles in various tissues during embryogenesis and after birth. We have previously generated a constitutively activated Acvr1(ca‐Acvr1) transgenic mouse line (line L35) through pronuclei injection to investigate impacts of enhanced BMP signaling in a tissue specific manner. However, line L35 shows a restricted expression pattern of the transgene. Here, we generated another ca‐Acvr1 transgenic line, line A11, using embryonic stem (ES) transgenesis. The generated line A11 shows distinctive phenotypes from line L35, along with very limited expression levels of the transgene. When the transgene is activated in the neural crest cells in a Cre‐dependent manner, line A11 exhibits cleft palate and shorter jaws, while line L35 develops ectopic cartilages and highly hypomorphic facial structures. When activated in limb buds, line A11 develops organized but smaller limb skeletal structures, while line L35 forms disorganized limbs with little mineralization. Additionally, no heterotopic ossification (HO) is identified in line A11 when bred with NFATc1‐Cre mice even after induction of tissue injury, which is an established protocol for HO for line L35. Therefore, the newly generated conditional ca‐Acvr1 mouse line A11 provides an additional resource to dissect highly context dependent functions of BMP signaling in development and disease. |
doi_str_mv | 10.1002/dvg.23419 |
format | Article |
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BMP signaling plays pleiotropic roles in various tissues during embryogenesis and after birth. We have previously generated a constitutively activated Acvr1(ca‐Acvr1) transgenic mouse line (line L35) through pronuclei injection to investigate impacts of enhanced BMP signaling in a tissue specific manner. However, line L35 shows a restricted expression pattern of the transgene. Here, we generated another ca‐Acvr1 transgenic line, line A11, using embryonic stem (ES) transgenesis. The generated line A11 shows distinctive phenotypes from line L35, along with very limited expression levels of the transgene. When the transgene is activated in the neural crest cells in a Cre‐dependent manner, line A11 exhibits cleft palate and shorter jaws, while line L35 develops ectopic cartilages and highly hypomorphic facial structures. When activated in limb buds, line A11 develops organized but smaller limb skeletal structures, while line L35 forms disorganized limbs with little mineralization. Additionally, no heterotopic ossification (HO) is identified in line A11 when bred with NFATc1‐Cre mice even after induction of tissue injury, which is an established protocol for HO for line L35. Therefore, the newly generated conditional ca‐Acvr1 mouse line A11 provides an additional resource to dissect highly context dependent functions of BMP signaling in development and disease.</description><identifier>ISSN: 1526-954X</identifier><identifier>EISSN: 1526-968X</identifier><identifier>DOI: 10.1002/dvg.23419</identifier><identifier>PMID: 33851764</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Activin Receptors, Type I - genetics ; Activin Receptors, Type I - metabolism ; Animals ; BMP signaling ; Bone Morphogenetic Proteins - metabolism ; caALK2 ; Cartilage - metabolism ; Chondrogenesis ; Cleft lip/palate ; Embryogenesis ; Embryonic growth stage ; Gene Targeting - methods ; Genetic Pleiotropy ; Limb buds ; Limb Buds - embryology ; Limb Buds - metabolism ; Mice ; Mice, Inbred C57BL ; Mineralization ; Neural crest ; orofacial development ; Ossification (ectopic) ; palatogenesis ; Phenotypes ; Signal Transduction ; Signaling ; skeletogenesis ; Tissues ; Transcriptional Activation ; Transgenes ; Transgenic mice</subject><ispartof>Genesis (New York, N.Y. : 2000), 2021-06, Vol.59 (5-6), p.e23419-n/a</ispartof><rights>2021 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4439-57c817dc679a1781ecf819564b2dae73ceea2840a60f82d30fe617594db62f503</citedby><cites>FETCH-LOGICAL-c4439-57c817dc679a1781ecf819564b2dae73ceea2840a60f82d30fe617594db62f503</cites><orcidid>0000-0002-6268-4204</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fdvg.23419$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fdvg.23419$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33851764$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Jingwen</creatorcontrib><creatorcontrib>Toda Nakamura, Masako</creatorcontrib><creatorcontrib>Hallett, Shawn A.</creatorcontrib><creatorcontrib>Ueharu, Hiroki</creatorcontrib><creatorcontrib>Zhang, Honghao</creatorcontrib><creatorcontrib>Kelley, Kristen</creatorcontrib><creatorcontrib>Fukuda, Tomokazu</creatorcontrib><creatorcontrib>Komatsu, Yoshihiro</creatorcontrib><creatorcontrib>Mishina, Yuji</creatorcontrib><title>Generation of a new mouse line with conditionally activated signaling through the BMP receptor, ACVR1: A tool to characterize pleiotropic roles of BMP functions</title><title>Genesis (New York, N.Y. : 2000)</title><addtitle>Genesis</addtitle><description>Summary
BMP signaling plays pleiotropic roles in various tissues during embryogenesis and after birth. We have previously generated a constitutively activated Acvr1(ca‐Acvr1) transgenic mouse line (line L35) through pronuclei injection to investigate impacts of enhanced BMP signaling in a tissue specific manner. However, line L35 shows a restricted expression pattern of the transgene. Here, we generated another ca‐Acvr1 transgenic line, line A11, using embryonic stem (ES) transgenesis. The generated line A11 shows distinctive phenotypes from line L35, along with very limited expression levels of the transgene. When the transgene is activated in the neural crest cells in a Cre‐dependent manner, line A11 exhibits cleft palate and shorter jaws, while line L35 develops ectopic cartilages and highly hypomorphic facial structures. When activated in limb buds, line A11 develops organized but smaller limb skeletal structures, while line L35 forms disorganized limbs with little mineralization. Additionally, no heterotopic ossification (HO) is identified in line A11 when bred with NFATc1‐Cre mice even after induction of tissue injury, which is an established protocol for HO for line L35. Therefore, the newly generated conditional ca‐Acvr1 mouse line A11 provides an additional resource to dissect highly context dependent functions of BMP signaling in development and disease.</description><subject>Activin Receptors, Type I - genetics</subject><subject>Activin Receptors, Type I - metabolism</subject><subject>Animals</subject><subject>BMP signaling</subject><subject>Bone Morphogenetic Proteins - metabolism</subject><subject>caALK2</subject><subject>Cartilage - metabolism</subject><subject>Chondrogenesis</subject><subject>Cleft lip/palate</subject><subject>Embryogenesis</subject><subject>Embryonic growth stage</subject><subject>Gene Targeting - methods</subject><subject>Genetic Pleiotropy</subject><subject>Limb buds</subject><subject>Limb Buds - embryology</subject><subject>Limb Buds - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mineralization</subject><subject>Neural crest</subject><subject>orofacial development</subject><subject>Ossification (ectopic)</subject><subject>palatogenesis</subject><subject>Phenotypes</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>skeletogenesis</subject><subject>Tissues</subject><subject>Transcriptional Activation</subject><subject>Transgenes</subject><subject>Transgenic mice</subject><issn>1526-954X</issn><issn>1526-968X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kd1qFDEYhgdR7I8eeAMS8MSC2yaZzGSmB8K66ipUFNHSs5DNfDOTkk3GJLPLejVeqpluW1TwJAnJw5OX782yZwSfEozpWbPpTmnOSP0gOyQFLWd1WV09vDsX7OogOwrhGmNcVJQ-zg7yvCoIL9lh9msJFryM2lnkWiSRhS1auzEAMtoC2urYI-VsoydEGrNDUkW9kREaFHSXrrTtUOy9G7s-7YDefPqCPCgYovOv0Hxx-ZWcozmKzpm0INVLnxTg9U9AgwHtoneDVsg7A2EKMQna0arpx_Ake9RKE-Dp7X6cfX__7tviw-zi8_LjYn4xU4zl9azgqiK8USWvJeEVAdVWpC5KtqKNBJ4rAEkrhmWJ24o2OW6hJLyoWbMqaVvg_Dh7vfcO42oNjQIbvTRi8Hot_U44qcXfL1b3onMbUVFcYpYnwctbgXc_RghRrHVQYIy0kOYpaEEop3VOeUJf_INeu9GnUU4Uwxyz-ibRyZ5S3oXgob0PQ7CYehepd3HTe2Kf_5n-nrwrOgFne2CrDez-bxJvL5d75W_eO7nE</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Yang, Jingwen</creator><creator>Toda Nakamura, Masako</creator><creator>Hallett, Shawn A.</creator><creator>Ueharu, Hiroki</creator><creator>Zhang, Honghao</creator><creator>Kelley, Kristen</creator><creator>Fukuda, Tomokazu</creator><creator>Komatsu, Yoshihiro</creator><creator>Mishina, Yuji</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6268-4204</orcidid></search><sort><creationdate>202106</creationdate><title>Generation of a new mouse line with conditionally activated signaling through the BMP receptor, ACVR1: A tool to characterize pleiotropic roles of BMP functions</title><author>Yang, Jingwen ; Toda Nakamura, Masako ; Hallett, Shawn A. ; Ueharu, Hiroki ; Zhang, Honghao ; Kelley, Kristen ; Fukuda, Tomokazu ; Komatsu, Yoshihiro ; Mishina, Yuji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4439-57c817dc679a1781ecf819564b2dae73ceea2840a60f82d30fe617594db62f503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Activin Receptors, Type I - genetics</topic><topic>Activin Receptors, Type I - metabolism</topic><topic>Animals</topic><topic>BMP signaling</topic><topic>Bone Morphogenetic Proteins - metabolism</topic><topic>caALK2</topic><topic>Cartilage - metabolism</topic><topic>Chondrogenesis</topic><topic>Cleft lip/palate</topic><topic>Embryogenesis</topic><topic>Embryonic growth stage</topic><topic>Gene Targeting - methods</topic><topic>Genetic Pleiotropy</topic><topic>Limb buds</topic><topic>Limb Buds - embryology</topic><topic>Limb Buds - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mineralization</topic><topic>Neural crest</topic><topic>orofacial development</topic><topic>Ossification (ectopic)</topic><topic>palatogenesis</topic><topic>Phenotypes</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>skeletogenesis</topic><topic>Tissues</topic><topic>Transcriptional Activation</topic><topic>Transgenes</topic><topic>Transgenic mice</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Jingwen</creatorcontrib><creatorcontrib>Toda Nakamura, Masako</creatorcontrib><creatorcontrib>Hallett, Shawn A.</creatorcontrib><creatorcontrib>Ueharu, Hiroki</creatorcontrib><creatorcontrib>Zhang, Honghao</creatorcontrib><creatorcontrib>Kelley, Kristen</creatorcontrib><creatorcontrib>Fukuda, Tomokazu</creatorcontrib><creatorcontrib>Komatsu, Yoshihiro</creatorcontrib><creatorcontrib>Mishina, Yuji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genesis (New York, N.Y. : 2000)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Jingwen</au><au>Toda Nakamura, Masako</au><au>Hallett, Shawn A.</au><au>Ueharu, Hiroki</au><au>Zhang, Honghao</au><au>Kelley, Kristen</au><au>Fukuda, Tomokazu</au><au>Komatsu, Yoshihiro</au><au>Mishina, Yuji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Generation of a new mouse line with conditionally activated signaling through the BMP receptor, ACVR1: A tool to characterize pleiotropic roles of BMP functions</atitle><jtitle>Genesis (New York, N.Y. : 2000)</jtitle><addtitle>Genesis</addtitle><date>2021-06</date><risdate>2021</risdate><volume>59</volume><issue>5-6</issue><spage>e23419</spage><epage>n/a</epage><pages>e23419-n/a</pages><issn>1526-954X</issn><eissn>1526-968X</eissn><abstract>Summary
BMP signaling plays pleiotropic roles in various tissues during embryogenesis and after birth. We have previously generated a constitutively activated Acvr1(ca‐Acvr1) transgenic mouse line (line L35) through pronuclei injection to investigate impacts of enhanced BMP signaling in a tissue specific manner. However, line L35 shows a restricted expression pattern of the transgene. Here, we generated another ca‐Acvr1 transgenic line, line A11, using embryonic stem (ES) transgenesis. The generated line A11 shows distinctive phenotypes from line L35, along with very limited expression levels of the transgene. When the transgene is activated in the neural crest cells in a Cre‐dependent manner, line A11 exhibits cleft palate and shorter jaws, while line L35 develops ectopic cartilages and highly hypomorphic facial structures. When activated in limb buds, line A11 develops organized but smaller limb skeletal structures, while line L35 forms disorganized limbs with little mineralization. Additionally, no heterotopic ossification (HO) is identified in line A11 when bred with NFATc1‐Cre mice even after induction of tissue injury, which is an established protocol for HO for line L35. Therefore, the newly generated conditional ca‐Acvr1 mouse line A11 provides an additional resource to dissect highly context dependent functions of BMP signaling in development and disease.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>33851764</pmid><doi>10.1002/dvg.23419</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-6268-4204</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Activin Receptors, Type I - genetics Activin Receptors, Type I - metabolism Animals BMP signaling Bone Morphogenetic Proteins - metabolism caALK2 Cartilage - metabolism Chondrogenesis Cleft lip/palate Embryogenesis Embryonic growth stage Gene Targeting - methods Genetic Pleiotropy Limb buds Limb Buds - embryology Limb Buds - metabolism Mice Mice, Inbred C57BL Mineralization Neural crest orofacial development Ossification (ectopic) palatogenesis Phenotypes Signal Transduction Signaling skeletogenesis Tissues Transcriptional Activation Transgenes Transgenic mice |
title | Generation of a new mouse line with conditionally activated signaling through the BMP receptor, ACVR1: A tool to characterize pleiotropic roles of BMP functions |
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