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Targeted microRNA expression in dairy cattle directs production of ?-lactoglobulin-free, high-casein milk.


ABSTRACT: Milk from dairy cows contains the protein ?-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.

SUBMITTER: Jabed A 

PROVIDER: S-EPMC3479461 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Targeted microRNA expression in dairy cattle directs production of β-lactoglobulin-free, high-casein milk.

Jabed Anower A   Wagner Stefan S   McCracken Judi J   Wells David N DN   Laible Goetz G  

Proceedings of the National Academy of Sciences of the United States of America 20121001 42


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 th  ...[more]

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