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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Veröffentlicht in:Genesis (New York, N.Y. : 2000) N.Y. : 2000), 2021-06, Vol.59 (5-6), p.e23419-n/a
Hauptverfasser: Yang, Jingwen, Toda Nakamura, Masako, Hallett, Shawn A., Ueharu, Hiroki, Zhang, Honghao, Kelley, Kristen, Fukuda, Tomokazu, Komatsu, Yoshihiro, Mishina, Yuji
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container_issue 5-6
container_start_page e23419
container_title Genesis (New York, N.Y. : 2000)
container_volume 59
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
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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 &amp; 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. 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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 &amp; 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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source MEDLINE; Wiley Online Library Journals Frontfile Complete
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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