Genetic analysis of Down syndrome-associated heart defects in mice
Human trisomy 21, the chromosomal basis of Down syndrome (DS), is the most common genetic cause of heart defects. Regions on human chromosome 21 (Hsa21) are syntenically conserved with three regions located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. In this study, we have analyzed the impact o...
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| Veröffentlicht in: | Human genetics 2011-11, Vol.130 (5), p.623-632 |
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| creator | Liu, Chunhong Morishima, Masae Yu, Tao Matsui, Sei-Ichi Zhang, Li Fu, Dawei Pao, Annie Costa, Alberto C. Gardiner, Katheleen J. Cowell, John K. Nowak, Normal J. Parmacek, Michael S. Liang, Ping Baldini, Antonio Yu, Y. Eugene |
| description | Human trisomy 21, the chromosomal basis of Down syndrome (DS), is the most common genetic cause of heart defects. Regions on human chromosome 21 (Hsa21) are syntenically conserved with three regions located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. In this study, we have analyzed the impact of duplications of each syntenic region on cardiovascular development in mice and have found that only the duplication on Mmu16, i.e.,
Dp(16)1Yey
, is associated with heart defects. Furthermore, we generated two novel mouse models carrying a 5.43-Mb duplication and a reciprocal deletion between
Tiam1
and
Kcnj6
using chromosome engineering,
Dp(16Tiam1
-
Kcnj6)Yey/
+ and
Df(16Tiam1
-
Kcnj6)Yey/
+, respectively, within the 22.9-Mb syntenic region on Mmu16. We found that
Dp(16Tiam1
-
Kcnj6)Yey
/+, but not
Dp(16)1Yey/Df(16Tiam1
-
Kcnj6)Yey
, resulted in heart defects, indicating that triplication of the
Tiam1
-
Knj6
region is necessary and sufficient to cause DS-associated heart defects. Our transcriptional analysis of
Dp(16Tiam1
-
Kcnj6)Yey
/+ embryos confirmed elevated expression levels for the genes located in the
Tiam
-
Kcnj6
region. Therefore, we established the smallest critical genomic region for DS-associated heart defects to lay the foundation for identifying the causative gene(s) for this phenotype. |
| doi_str_mv | 10.1007/s00439-011-0980-2 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3257027</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A364958246</galeid><sourcerecordid>A364958246</sourcerecordid><originalsourceid>FETCH-LOGICAL-c697t-5421c4d75a7a49f64fe425c37da277c52526d380e1cff75c2360b86038ae23613</originalsourceid><addsrcrecordid>eNp1kl1rFDEYhQdR7Fr9Ad7IoIh4MTXfmbkRatVaKAh-XIc082abMpvUvDPq_nszzNq6ogSSkDznvHA4VfWYkiNKiH6FhAjeNYTShnQtadidakUFZw1lhN-tVoQL0ihN9UH1APGKECo7Ju9XB4wKwTjrVtWbU4gwBlfbaIctBqyTr9-mH7HGbexz2kBjEZMLdoS-vgSbx7oHD27EOsR6Exw8rO55OyA82p2H1df3776cfGjOP56enRyfN051emykYNSJXkurrei8Eh4Ek47r3jKtnWSSqZ63BKjzXkvHuCIXrSK8tVDulB9Wrxff6-liA72DOGY7mOscNjZvTbLB7P_EcGnW6bvhTGrCdDF4sTPI6dsEOJpNQAfDYCOkCU3HVNsRJkUhn_5FXqUpl4TQtF1LtSpbgZ4t0NoOYEL0qUx1s6U55kp0smVCFeroH1RZPZTwUgQfyvue4OWeoDAj_BzXdkI0Z58_7bN0YV1OiBn8TRqUmLkiZqmIKRUxc0UMK5onf8Z4o_jdiQI83wEWnR18ttEFvOWEmms0G7GFw_IV15BvQ_r_9F-07NAQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>898176981</pqid></control><display><type>article</type><title>Genetic analysis of Down syndrome-associated heart defects in mice</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Liu, Chunhong ; Morishima, Masae ; Yu, Tao ; Matsui, Sei-Ichi ; Zhang, Li ; Fu, Dawei ; Pao, Annie ; Costa, Alberto C. ; Gardiner, Katheleen J. ; Cowell, John K. ; Nowak, Normal J. ; Parmacek, Michael S. ; Liang, Ping ; Baldini, Antonio ; Yu, Y. Eugene</creator><creatorcontrib>Liu, Chunhong ; Morishima, Masae ; Yu, Tao ; Matsui, Sei-Ichi ; Zhang, Li ; Fu, Dawei ; Pao, Annie ; Costa, Alberto C. ; Gardiner, Katheleen J. ; Cowell, John K. ; Nowak, Normal J. ; Parmacek, Michael S. ; Liang, Ping ; Baldini, Antonio ; Yu, Y. Eugene</creatorcontrib><description>Human trisomy 21, the chromosomal basis of Down syndrome (DS), is the most common genetic cause of heart defects. Regions on human chromosome 21 (Hsa21) are syntenically conserved with three regions located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. In this study, we have analyzed the impact of duplications of each syntenic region on cardiovascular development in mice and have found that only the duplication on Mmu16, i.e.,
Dp(16)1Yey
, is associated with heart defects. Furthermore, we generated two novel mouse models carrying a 5.43-Mb duplication and a reciprocal deletion between
Tiam1
and
Kcnj6
using chromosome engineering,
Dp(16Tiam1
-
Kcnj6)Yey/
+ and
Df(16Tiam1
-
Kcnj6)Yey/
+, respectively, within the 22.9-Mb syntenic region on Mmu16. We found that
Dp(16Tiam1
-
Kcnj6)Yey
/+, but not
Dp(16)1Yey/Df(16Tiam1
-
Kcnj6)Yey
, resulted in heart defects, indicating that triplication of the
Tiam1
-
Knj6
region is necessary and sufficient to cause DS-associated heart defects. Our transcriptional analysis of
Dp(16Tiam1
-
Kcnj6)Yey
/+ embryos confirmed elevated expression levels for the genes located in the
Tiam
-
Kcnj6
region. Therefore, we established the smallest critical genomic region for DS-associated heart defects to lay the foundation for identifying the causative gene(s) for this phenotype.</description><identifier>ISSN: 0340-6717</identifier><identifier>EISSN: 1432-1203</identifier><identifier>DOI: 10.1007/s00439-011-0980-2</identifier><identifier>PMID: 21442329</identifier><identifier>CODEN: HUGEDQ</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Analysis ; Animal models ; Animals ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Cardiovascular disease ; chromosome 10 ; chromosome 21 ; Chromosome aberrations ; Chromosome deletion ; Chromosomes ; Classical genetics, quantitative genetics, hybrids ; Congenital diseases ; Disease Models, Animal ; Down syndrome ; Down Syndrome - genetics ; Down's syndrome ; Embryos ; Female ; Fundamental and applied biological sciences. Psychology ; G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics ; Gene Duplication - genetics ; Gene Function ; Genetic analysis ; Genetic aspects ; Genetics of eukaryotes. Biological and molecular evolution ; genomics ; Guanine Nucleotide Exchange Factors - genetics ; Heart ; Heart Defects, Congenital - genetics ; Human ; Human Genetics ; Male ; Medical genetics ; Medical sciences ; Metabolic Diseases ; Mice ; Mice, Mutant Strains ; Molecular Medicine ; Original Investigation ; Sequence Deletion - genetics ; Synteny ; Synteny - genetics ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; Tiam1 protein ; Transcription ; Trisomy</subject><ispartof>Human genetics, 2011-11, Vol.130 (5), p.623-632</ispartof><rights>Springer-Verlag 2011</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2011 Springer</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c697t-5421c4d75a7a49f64fe425c37da277c52526d380e1cff75c2360b86038ae23613</citedby><cites>FETCH-LOGICAL-c697t-5421c4d75a7a49f64fe425c37da277c52526d380e1cff75c2360b86038ae23613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00439-011-0980-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00439-011-0980-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24615922$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21442329$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Chunhong</creatorcontrib><creatorcontrib>Morishima, Masae</creatorcontrib><creatorcontrib>Yu, Tao</creatorcontrib><creatorcontrib>Matsui, Sei-Ichi</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Fu, Dawei</creatorcontrib><creatorcontrib>Pao, Annie</creatorcontrib><creatorcontrib>Costa, Alberto C.</creatorcontrib><creatorcontrib>Gardiner, Katheleen J.</creatorcontrib><creatorcontrib>Cowell, John K.</creatorcontrib><creatorcontrib>Nowak, Normal J.</creatorcontrib><creatorcontrib>Parmacek, Michael S.</creatorcontrib><creatorcontrib>Liang, Ping</creatorcontrib><creatorcontrib>Baldini, Antonio</creatorcontrib><creatorcontrib>Yu, Y. Eugene</creatorcontrib><title>Genetic analysis of Down syndrome-associated heart defects in mice</title><title>Human genetics</title><addtitle>Hum Genet</addtitle><addtitle>Hum Genet</addtitle><description>Human trisomy 21, the chromosomal basis of Down syndrome (DS), is the most common genetic cause of heart defects. Regions on human chromosome 21 (Hsa21) are syntenically conserved with three regions located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. In this study, we have analyzed the impact of duplications of each syntenic region on cardiovascular development in mice and have found that only the duplication on Mmu16, i.e.,
Dp(16)1Yey
, is associated with heart defects. Furthermore, we generated two novel mouse models carrying a 5.43-Mb duplication and a reciprocal deletion between
Tiam1
and
Kcnj6
using chromosome engineering,
Dp(16Tiam1
-
Kcnj6)Yey/
+ and
Df(16Tiam1
-
Kcnj6)Yey/
+, respectively, within the 22.9-Mb syntenic region on Mmu16. We found that
Dp(16Tiam1
-
Kcnj6)Yey
/+, but not
Dp(16)1Yey/Df(16Tiam1
-
Kcnj6)Yey
, resulted in heart defects, indicating that triplication of the
Tiam1
-
Knj6
region is necessary and sufficient to cause DS-associated heart defects. Our transcriptional analysis of
Dp(16Tiam1
-
Kcnj6)Yey
/+ embryos confirmed elevated expression levels for the genes located in the
Tiam
-
Kcnj6
region. Therefore, we established the smallest critical genomic region for DS-associated heart defects to lay the foundation for identifying the causative gene(s) for this phenotype.</description><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cardiovascular disease</subject><subject>chromosome 10</subject><subject>chromosome 21</subject><subject>Chromosome aberrations</subject><subject>Chromosome deletion</subject><subject>Chromosomes</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>Congenital diseases</subject><subject>Disease Models, Animal</subject><subject>Down syndrome</subject><subject>Down Syndrome - genetics</subject><subject>Down's syndrome</subject><subject>Embryos</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics</subject><subject>Gene Duplication - genetics</subject><subject>Gene Function</subject><subject>Genetic analysis</subject><subject>Genetic aspects</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>genomics</subject><subject>Guanine Nucleotide Exchange Factors - genetics</subject><subject>Heart</subject><subject>Heart Defects, Congenital - genetics</subject><subject>Human</subject><subject>Human Genetics</subject><subject>Male</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Metabolic Diseases</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>Molecular Medicine</subject><subject>Original Investigation</subject><subject>Sequence Deletion - genetics</subject><subject>Synteny</subject><subject>Synteny - genetics</subject><subject>T-Lymphoma Invasion and Metastasis-inducing Protein 1</subject><subject>Tiam1 protein</subject><subject>Transcription</subject><subject>Trisomy</subject><issn>0340-6717</issn><issn>1432-1203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kl1rFDEYhQdR7Fr9Ad7IoIh4MTXfmbkRatVaKAh-XIc082abMpvUvDPq_nszzNq6ogSSkDznvHA4VfWYkiNKiH6FhAjeNYTShnQtadidakUFZw1lhN-tVoQL0ihN9UH1APGKECo7Ju9XB4wKwTjrVtWbU4gwBlfbaIctBqyTr9-mH7HGbexz2kBjEZMLdoS-vgSbx7oHD27EOsR6Exw8rO55OyA82p2H1df3776cfGjOP56enRyfN051emykYNSJXkurrei8Eh4Ek47r3jKtnWSSqZ63BKjzXkvHuCIXrSK8tVDulB9Wrxff6-liA72DOGY7mOscNjZvTbLB7P_EcGnW6bvhTGrCdDF4sTPI6dsEOJpNQAfDYCOkCU3HVNsRJkUhn_5FXqUpl4TQtF1LtSpbgZ4t0NoOYEL0qUx1s6U55kp0smVCFeroH1RZPZTwUgQfyvue4OWeoDAj_BzXdkI0Z58_7bN0YV1OiBn8TRqUmLkiZqmIKRUxc0UMK5onf8Z4o_jdiQI83wEWnR18ttEFvOWEmms0G7GFw_IV15BvQ_r_9F-07NAQ</recordid><startdate>20111101</startdate><enddate>20111101</enddate><creator>Liu, Chunhong</creator><creator>Morishima, Masae</creator><creator>Yu, Tao</creator><creator>Matsui, Sei-Ichi</creator><creator>Zhang, Li</creator><creator>Fu, Dawei</creator><creator>Pao, Annie</creator><creator>Costa, Alberto C.</creator><creator>Gardiner, Katheleen J.</creator><creator>Cowell, John K.</creator><creator>Nowak, Normal J.</creator><creator>Parmacek, Michael S.</creator><creator>Liang, Ping</creator><creator>Baldini, Antonio</creator><creator>Yu, Y. Eugene</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20111101</creationdate><title>Genetic analysis of Down syndrome-associated heart defects in mice</title><author>Liu, Chunhong ; Morishima, Masae ; Yu, Tao ; Matsui, Sei-Ichi ; Zhang, Li ; Fu, Dawei ; Pao, Annie ; Costa, Alberto C. ; Gardiner, Katheleen J. ; Cowell, John K. ; Nowak, Normal J. ; Parmacek, Michael S. ; Liang, Ping ; Baldini, Antonio ; Yu, Y. Eugene</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c697t-5421c4d75a7a49f64fe425c37da277c52526d380e1cff75c2360b86038ae23613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Cardiovascular disease</topic><topic>chromosome 10</topic><topic>chromosome 21</topic><topic>Chromosome aberrations</topic><topic>Chromosome deletion</topic><topic>Chromosomes</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>Congenital diseases</topic><topic>Disease Models, Animal</topic><topic>Down syndrome</topic><topic>Down Syndrome - genetics</topic><topic>Down's syndrome</topic><topic>Embryos</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics</topic><topic>Gene Duplication - genetics</topic><topic>Gene Function</topic><topic>Genetic analysis</topic><topic>Genetic aspects</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>genomics</topic><topic>Guanine Nucleotide Exchange Factors - genetics</topic><topic>Heart</topic><topic>Heart Defects, Congenital - genetics</topic><topic>Human</topic><topic>Human Genetics</topic><topic>Male</topic><topic>Medical genetics</topic><topic>Medical sciences</topic><topic>Metabolic Diseases</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>Molecular Medicine</topic><topic>Original Investigation</topic><topic>Sequence Deletion - genetics</topic><topic>Synteny</topic><topic>Synteny - genetics</topic><topic>T-Lymphoma Invasion and Metastasis-inducing Protein 1</topic><topic>Tiam1 protein</topic><topic>Transcription</topic><topic>Trisomy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Chunhong</creatorcontrib><creatorcontrib>Morishima, Masae</creatorcontrib><creatorcontrib>Yu, Tao</creatorcontrib><creatorcontrib>Matsui, Sei-Ichi</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Fu, Dawei</creatorcontrib><creatorcontrib>Pao, Annie</creatorcontrib><creatorcontrib>Costa, Alberto C.</creatorcontrib><creatorcontrib>Gardiner, Katheleen J.</creatorcontrib><creatorcontrib>Cowell, John K.</creatorcontrib><creatorcontrib>Nowak, Normal J.</creatorcontrib><creatorcontrib>Parmacek, Michael S.</creatorcontrib><creatorcontrib>Liang, Ping</creatorcontrib><creatorcontrib>Baldini, Antonio</creatorcontrib><creatorcontrib>Yu, Y. Eugene</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Chunhong</au><au>Morishima, Masae</au><au>Yu, Tao</au><au>Matsui, Sei-Ichi</au><au>Zhang, Li</au><au>Fu, Dawei</au><au>Pao, Annie</au><au>Costa, Alberto C.</au><au>Gardiner, Katheleen J.</au><au>Cowell, John K.</au><au>Nowak, Normal J.</au><au>Parmacek, Michael S.</au><au>Liang, Ping</au><au>Baldini, Antonio</au><au>Yu, Y. Eugene</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic analysis of Down syndrome-associated heart defects in mice</atitle><jtitle>Human genetics</jtitle><stitle>Hum Genet</stitle><addtitle>Hum Genet</addtitle><date>2011-11-01</date><risdate>2011</risdate><volume>130</volume><issue>5</issue><spage>623</spage><epage>632</epage><pages>623-632</pages><issn>0340-6717</issn><eissn>1432-1203</eissn><coden>HUGEDQ</coden><abstract>Human trisomy 21, the chromosomal basis of Down syndrome (DS), is the most common genetic cause of heart defects. Regions on human chromosome 21 (Hsa21) are syntenically conserved with three regions located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. In this study, we have analyzed the impact of duplications of each syntenic region on cardiovascular development in mice and have found that only the duplication on Mmu16, i.e.,
Dp(16)1Yey
, is associated with heart defects. Furthermore, we generated two novel mouse models carrying a 5.43-Mb duplication and a reciprocal deletion between
Tiam1
and
Kcnj6
using chromosome engineering,
Dp(16Tiam1
-
Kcnj6)Yey/
+ and
Df(16Tiam1
-
Kcnj6)Yey/
+, respectively, within the 22.9-Mb syntenic region on Mmu16. We found that
Dp(16Tiam1
-
Kcnj6)Yey
/+, but not
Dp(16)1Yey/Df(16Tiam1
-
Kcnj6)Yey
, resulted in heart defects, indicating that triplication of the
Tiam1
-
Knj6
region is necessary and sufficient to cause DS-associated heart defects. Our transcriptional analysis of
Dp(16Tiam1
-
Kcnj6)Yey
/+ embryos confirmed elevated expression levels for the genes located in the
Tiam
-
Kcnj6
region. Therefore, we established the smallest critical genomic region for DS-associated heart defects to lay the foundation for identifying the causative gene(s) for this phenotype.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>21442329</pmid><doi>10.1007/s00439-011-0980-2</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-6717 |
| ispartof | Human genetics, 2011-11, Vol.130 (5), p.623-632 |
| issn | 0340-6717 1432-1203 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3257027 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Analysis Animal models Animals Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Cardiovascular disease chromosome 10 chromosome 21 Chromosome aberrations Chromosome deletion Chromosomes Classical genetics, quantitative genetics, hybrids Congenital diseases Disease Models, Animal Down syndrome Down Syndrome - genetics Down's syndrome Embryos Female Fundamental and applied biological sciences. Psychology G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics Gene Duplication - genetics Gene Function Genetic analysis Genetic aspects Genetics of eukaryotes. Biological and molecular evolution genomics Guanine Nucleotide Exchange Factors - genetics Heart Heart Defects, Congenital - genetics Human Human Genetics Male Medical genetics Medical sciences Metabolic Diseases Mice Mice, Mutant Strains Molecular Medicine Original Investigation Sequence Deletion - genetics Synteny Synteny - genetics T-Lymphoma Invasion and Metastasis-inducing Protein 1 Tiam1 protein Transcription Trisomy |
| title | Genetic analysis of Down syndrome-associated heart defects in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T15%3A57%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20analysis%20of%20Down%20syndrome-associated%20heart%20defects%20in%20mice&rft.jtitle=Human%20genetics&rft.au=Liu,%20Chunhong&rft.date=2011-11-01&rft.volume=130&rft.issue=5&rft.spage=623&rft.epage=632&rft.pages=623-632&rft.issn=0340-6717&rft.eissn=1432-1203&rft.coden=HUGEDQ&rft_id=info:doi/10.1007/s00439-011-0980-2&rft_dat=%3Cgale_pubme%3EA364958246%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=898176981&rft_id=info:pmid/21442329&rft_galeid=A364958246&rfr_iscdi=true |