YEARS

2003-2008

AUTHORS

Ina Dobrinski

TITLE

Transgenic Goats Produced by Germ Cell Transplantation

ABSTRACT

DESCRIPTION (provided by applicant): The objective of this proposal is to produce transgenic goats by manipulation of the male germ line through male germ cell transfection and transplantation. The goats will carry the gene for human growth hormone (rhGH) under the control of a mammary gland specific promoter such that the milk of transgenic females will be an efficient source of protein for purification of human growth hormone. The milk of transgenic goats is a safe, abundant and cost effective production source for recombinant human biopharmaceuticals. GTC Biotherapeutics (formerly Genzyme Transgenics Corp.) has nearly two dozen commercial transgenic programs in development. However, even state-of-the-art methods for generating transgenic founder (first generation) goats remain relatively inefficient and expensive. Methods have been developed in rodents for transplanting genetically modified male germ cells into recipient males and mating these animals to produce transgenic offspring. During phase I of this project we successfully adapted the systems of germ cell transfection and transplantation to goats and demonstrated feasibility that recipient goats produce offspring carrying the genetic makeup of the germ cell donor animal. Now we propose to: 1) produce goats making transgenic sperm after transplantation of transfected germ cells; 2) generate transgenic embryos by in vitro fertilization and produce live transgenic offspring carrying expressing a commercially significant protein in their milk; and 3) establish a system for caprine germ cell culture to make the approach universally applicable to a wider range of transgene constructs. Successful introduction of a transgene through the male germ line will increase the efficiency and reduce the cost of generating founder animals, which is a critical early step in the transgenic production process.

FUNDED PUBLICATIONS

  • Adeno-associated virus (AAV)-mediated transduction of male germ line stem cells results in transgene transmission after germ cell transplantation.
  • Establishment of goat embryonic stem cells from in vivo produced blastocyst-stage embryos.
  • Germ cell transplantation for the propagation of companion animals, non-domestic and endangered species.
  • Male germ cell transplantation.
  • Non-viral transfection of goat germline stem cells by nucleofection results in production of transgenic sperm after germ cell transplantation.
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    22 TRIPLES      17 PREDICATES      23 URIs      9 LITERALS

    Subject Predicate Object
    1 grants:a80d34223ae417be8ee404a5fd67d8aa sg:abstract DESCRIPTION (provided by applicant): The objective of this proposal is to produce transgenic goats by manipulation of the male germ line through male germ cell transfection and transplantation. The goats will carry the gene for human growth hormone (rhGH) under the control of a mammary gland specific promoter such that the milk of transgenic females will be an efficient source of protein for purification of human growth hormone. The milk of transgenic goats is a safe, abundant and cost effective production source for recombinant human biopharmaceuticals. GTC Biotherapeutics (formerly Genzyme Transgenics Corp.) has nearly two dozen commercial transgenic programs in development. However, even state-of-the-art methods for generating transgenic founder (first generation) goats remain relatively inefficient and expensive. Methods have been developed in rodents for transplanting genetically modified male germ cells into recipient males and mating these animals to produce transgenic offspring. During phase I of this project we successfully adapted the systems of germ cell transfection and transplantation to goats and demonstrated feasibility that recipient goats produce offspring carrying the genetic makeup of the germ cell donor animal. Now we propose to: 1) produce goats making transgenic sperm after transplantation of transfected germ cells; 2) generate transgenic embryos by in vitro fertilization and produce live transgenic offspring carrying expressing a commercially significant protein in their milk; and 3) establish a system for caprine germ cell culture to make the approach universally applicable to a wider range of transgene constructs. Successful introduction of a transgene through the male germ line will increase the efficiency and reduce the cost of generating founder animals, which is a critical early step in the transgenic production process.
    2 sg:endYear 2008
    3 sg:fundingAmount 748655.0
    4 sg:fundingCurrency USD
    5 sg:hasContribution contributions:af498f02fd4e11d2de1d4edc189fa0de
    6 sg:hasFieldOfResearchCode anzsrc-for:06
    7 anzsrc-for:0604
    8 sg:hasFundedPublication articles:0fbfbb982901bf79d6b83fbddc988cb4
    9 articles:278eacb0d3e8e5a53dbce6ae905644c5
    10 articles:3f3eecafca2cfa46a2c6fa3ade5518e8
    11 articles:a506c0890a720d8447ed77c013993bfd
    12 articles:ff7969b9cdd06a676ebded7be51af25e
    13 sg:hasFundingOrganization grid-institutes:grid.420089.7
    14 sg:hasRecipientOrganization grid-institutes:grid.420525.4
    15 sg:language English
    16 sg:license http://scigraph.springernature.com/explorer/license/
    17 sg:scigraphId a80d34223ae417be8ee404a5fd67d8aa
    18 sg:startYear 2003
    19 sg:title Transgenic Goats Produced by Germ Cell Transplantation
    20 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=7067133
    21 rdf:type sg:Grant
    22 rdfs:label Grant: Transgenic Goats Produced by Germ Cell Transplantation
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