Targeted microRNA expression in dairy cattle directs production of β-lactoglobulin-free, high-casein milk
Milk from dairy cows contains the protein β-lactoglobulin (BLG), which is not present in human milk. As it is a major milk allergen, we wished to decrease BLG levels in milk by RNAi. In vitro screening of 10 microRNAs (miRNAs), either individually or in tandem combinations, identified several that a...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2012-10, Vol.109 (42), p.16811-16816 |
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| creator | Jabed, Anower Wagner, Stefan McCracken, Judi Wells, David N Laible, Goetz |
| description | Milk from dairy cows contains the protein β-lactoglobulin (BLG), which is not present in human milk. As it is a major milk allergen, we wished to decrease BLG levels in milk by RNAi. In vitro screening of 10 microRNAs (miRNAs), either individually or in tandem combinations, identified several that achieved as much as a 98% knockdown of BLG. One tandem construct was expressed in the mammary gland of an ovine BLG-expressing mouse model, resulting in 96% knockdown of ovine BLG in milk. Following this in vivo validation, we produced a transgenic calf, engineered to express these tandem miRNAs. Analysis of hormonally induced milk from this calf demonstrated absence of BLG and a concurrent increase of all casein milk proteins. The findings demonstrate miRNA–mediated depletion of an allergenic milk protein in cattle and validate targeted miRNA expression as an effective strategy to alter milk composition and other livestock traits. |
| doi_str_mv | 10.1073/pnas.1210057109 |
| format | Article |
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As it is a major milk allergen, we wished to decrease BLG levels in milk by RNAi. In vitro screening of 10 microRNAs (miRNAs), either individually or in tandem combinations, identified several that achieved as much as a 98% knockdown of BLG. One tandem construct was expressed in the mammary gland of an ovine BLG-expressing mouse model, resulting in 96% knockdown of ovine BLG in milk. Following this in vivo validation, we produced a transgenic calf, engineered to express these tandem miRNAs. Analysis of hormonally induced milk from this calf demonstrated absence of BLG and a concurrent increase of all casein milk proteins. The findings demonstrate miRNA–mediated depletion of an allergenic milk protein in cattle and validate targeted miRNA expression as an effective strategy to alter milk composition and other livestock traits.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1210057109</identifier><identifier>PMID: 23027958</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>allergenicity ; allergens ; animal models ; Animals ; Animals, Genetically Modified ; beta-lactoglobulin ; Biological Sciences ; Blotting, Western - veterinary ; breast milk ; calves ; casein ; Caseins - analysis ; Cattle - genetics ; Cercopithecus aethiops ; COS Cells ; Dairy cattle ; dairy cows ; dairy protein ; Dairying - methods ; Female ; Gene Knockdown Techniques - veterinary ; Lactation ; Lactoglobulins - analysis ; Lactoglobulins - genetics ; mammary glands ; Mice ; MicroRNA ; MicroRNAs - metabolism ; Milk ; Milk - chemistry ; Milk protein ; RNA Interference ; screening ; Sheep ; Transgenes ; Transgenic animals ; Ungulates</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2012-10, Vol.109 (42), p.16811-16816</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-3c58f45e8c300f78bb4cecd43c251ca2b39f2599135bb54de36a329ea13aac5b3</citedby><cites>FETCH-LOGICAL-c464t-3c58f45e8c300f78bb4cecd43c251ca2b39f2599135bb54de36a329ea13aac5b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/109/42.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41763443$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41763443$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23027958$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jabed, Anower</creatorcontrib><creatorcontrib>Wagner, Stefan</creatorcontrib><creatorcontrib>McCracken, Judi</creatorcontrib><creatorcontrib>Wells, David N</creatorcontrib><creatorcontrib>Laible, Goetz</creatorcontrib><title>Targeted microRNA expression in dairy cattle directs production of β-lactoglobulin-free, high-casein milk</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Milk from dairy cows contains the protein β-lactoglobulin (BLG), which is not present in human milk. As it is a major milk allergen, we wished to decrease BLG levels in milk by RNAi. In vitro screening of 10 microRNAs (miRNAs), either individually or in tandem combinations, identified several that achieved as much as a 98% knockdown of BLG. One tandem construct was expressed in the mammary gland of an ovine BLG-expressing mouse model, resulting in 96% knockdown of ovine BLG in milk. Following this in vivo validation, we produced a transgenic calf, engineered to express these tandem miRNAs. Analysis of hormonally induced milk from this calf demonstrated absence of BLG and a concurrent increase of all casein milk proteins. The findings demonstrate miRNA–mediated depletion of an allergenic milk protein in cattle and validate targeted miRNA expression as an effective strategy to alter milk composition and other livestock traits.</description><subject>allergenicity</subject><subject>allergens</subject><subject>animal models</subject><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>beta-lactoglobulin</subject><subject>Biological Sciences</subject><subject>Blotting, Western - veterinary</subject><subject>breast milk</subject><subject>calves</subject><subject>casein</subject><subject>Caseins - analysis</subject><subject>Cattle - genetics</subject><subject>Cercopithecus aethiops</subject><subject>COS Cells</subject><subject>Dairy cattle</subject><subject>dairy cows</subject><subject>dairy protein</subject><subject>Dairying - methods</subject><subject>Female</subject><subject>Gene Knockdown Techniques - veterinary</subject><subject>Lactation</subject><subject>Lactoglobulins - analysis</subject><subject>Lactoglobulins - genetics</subject><subject>mammary glands</subject><subject>Mice</subject><subject>MicroRNA</subject><subject>MicroRNAs - metabolism</subject><subject>Milk</subject><subject>Milk - chemistry</subject><subject>Milk protein</subject><subject>RNA Interference</subject><subject>screening</subject><subject>Sheep</subject><subject>Transgenes</subject><subject>Transgenic animals</subject><subject>Ungulates</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1u1TAQhS0EopfCmhXgJQvSemznb4NUVfxJFUjQri3HmeT6ksSp7SD6WjwIz4Sje7mFzXik883xaA4hz4GdASvF-TzpcAYcGMtLYPUDskkVskLW7CHZMMbLrJJcnpAnIewYY3VescfkhIukpH5Ddtfa9xixpaM13n39fEHx5-wxBOsmaifaauvvqNExDkhb69HEQGfv2sXEFXEd_f0rG7SJrh9cswx2yjqP-IZubb_NjA6YXEY7fH9KHnV6CPjs8J6Sm_fvri8_ZldfPny6vLjKjCxkzITJq07mWBnBWFdWTSMNmlYKw3Mwmjei7nhe1yDypslli6LQgteoQWht8kackrd733lpRmwNTtHrQc3ejtrfKaet-l-Z7Fb17ocSsqxlAcng9cHAu9sFQ1SjDQaHQU_olqAAQHCAWlQJPd-j6XYheOyO3wBTa0JqTUjdJ5QmXv673ZH_G0kC6AFYJ-_taiW5gqKCdcEXe2QXovNHRkJZCClF0l_t9U47pXtvg7r5xhkUjEE6KpfiD_GzrTw</recordid><startdate>20121016</startdate><enddate>20121016</enddate><creator>Jabed, Anower</creator><creator>Wagner, Stefan</creator><creator>McCracken, Judi</creator><creator>Wells, David N</creator><creator>Laible, Goetz</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20121016</creationdate><title>Targeted microRNA expression in dairy cattle directs production of β-lactoglobulin-free, high-casein milk</title><author>Jabed, Anower ; Wagner, Stefan ; McCracken, Judi ; Wells, David N ; Laible, Goetz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-3c58f45e8c300f78bb4cecd43c251ca2b39f2599135bb54de36a329ea13aac5b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>allergenicity</topic><topic>allergens</topic><topic>animal models</topic><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>beta-lactoglobulin</topic><topic>Biological Sciences</topic><topic>Blotting, Western - veterinary</topic><topic>breast milk</topic><topic>calves</topic><topic>casein</topic><topic>Caseins - analysis</topic><topic>Cattle - genetics</topic><topic>Cercopithecus aethiops</topic><topic>COS Cells</topic><topic>Dairy cattle</topic><topic>dairy cows</topic><topic>dairy protein</topic><topic>Dairying - methods</topic><topic>Female</topic><topic>Gene Knockdown Techniques - veterinary</topic><topic>Lactation</topic><topic>Lactoglobulins - analysis</topic><topic>Lactoglobulins - genetics</topic><topic>mammary glands</topic><topic>Mice</topic><topic>MicroRNA</topic><topic>MicroRNAs - metabolism</topic><topic>Milk</topic><topic>Milk - chemistry</topic><topic>Milk protein</topic><topic>RNA Interference</topic><topic>screening</topic><topic>Sheep</topic><topic>Transgenes</topic><topic>Transgenic animals</topic><topic>Ungulates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jabed, Anower</creatorcontrib><creatorcontrib>Wagner, Stefan</creatorcontrib><creatorcontrib>McCracken, Judi</creatorcontrib><creatorcontrib>Wells, David N</creatorcontrib><creatorcontrib>Laible, Goetz</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jabed, Anower</au><au>Wagner, Stefan</au><au>McCracken, Judi</au><au>Wells, David N</au><au>Laible, Goetz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted microRNA expression in dairy cattle directs production of β-lactoglobulin-free, high-casein milk</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2012-10-16</date><risdate>2012</risdate><volume>109</volume><issue>42</issue><spage>16811</spage><epage>16816</epage><pages>16811-16816</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Milk from dairy cows contains the protein β-lactoglobulin (BLG), which is not present in human milk. As it is a major milk allergen, we wished to decrease BLG levels in milk by RNAi. In vitro screening of 10 microRNAs (miRNAs), either individually or in tandem combinations, identified several that achieved as much as a 98% knockdown of BLG. One tandem construct was expressed in the mammary gland of an ovine BLG-expressing mouse model, resulting in 96% knockdown of ovine BLG in milk. Following this in vivo validation, we produced a transgenic calf, engineered to express these tandem miRNAs. Analysis of hormonally induced milk from this calf demonstrated absence of BLG and a concurrent increase of all casein milk proteins. 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| subjects | allergenicity allergens animal models Animals Animals, Genetically Modified beta-lactoglobulin Biological Sciences Blotting, Western - veterinary breast milk calves casein Caseins - analysis Cattle - genetics Cercopithecus aethiops COS Cells Dairy cattle dairy cows dairy protein Dairying - methods Female Gene Knockdown Techniques - veterinary Lactation Lactoglobulins - analysis Lactoglobulins - genetics mammary glands Mice MicroRNA MicroRNAs - metabolism Milk Milk - chemistry Milk protein RNA Interference screening Sheep Transgenes Transgenic animals Ungulates |
| title | Targeted microRNA expression in dairy cattle directs production of β-lactoglobulin-free, high-casein milk |
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