A cell based system for the production of transgenic animals would offer significant advantages, allowing in vitro analysis of transgenes before the production of whole animals, precise placement of transgenes and the possibility of deletion, replacement or mutation of endogenous genes. In mice embryonic stem cells provide a tool for such precise genetic manipulation. However, despite considerable efforts, neither ES nor EG cells capable of contributing to the germline of any livestock species have been isolated. This dissertation describes cell mediated transgenesis by in vitro transfection of cultured cells followed by nuclear transfer. Several different cell cultures were assessed for their suitability for nuclear transfer. Viable lambs were obtained from embryonic, fetal and adult somatic cells. This demonstrated for the first time that cellular totipotency is not irreversibly lost during differentiation. Some but not all of these cell types could support cell mediated transgenesis. A genomic Factor IX construct designed to express in the lactating mammary gland has been generated and used to demonstrate nuclear transfer as a means of transgenesis. Viable Factor IX transgenic female lambs were derived, and shown to express high concentration of the recombinant protein in their milk. These now provide the prospect of recombinant Factor IX as a safe alternative to human serum derived protein for the treatment of Haemophilia B. Also reported are preliminary experiments to assess gene targeting in farm animals. An ovine HPRT targeting vector was constructed. Inactivation of the ovine HPRT locus was attempted using fibroblast cells capable of supporting development after nuclear transfer.

An approach known as management strategy evaluation (MSE) provides a framework for identifying robust management strategies in the presence of multiple management objectives and system uncertainties, and has been increasingly used as a practical fisheries management framework in recent years. However, few examples exist that incorporate economics in MSEs. Meanwhile, there has been increased attention given to economic instruments for sustainable management of fishery resources, including the use of bioeconomic target reference points (RPs). However, investigation of the causes of errors and bias in the estimates of bioeconomic parameters is scarcely documented compared to their biological counterparts, and the implications of simplified assumptions concerning both the biological and economic parts of the bioeconomic models have not been adequately investigated. In this thesis, I used three case study fisheries to illustrate how economics can be explicitly integrated within the MSE framework, and demonstrated the usefulness of this flexible approach as a rigorous tool for the evaluation of the effect of uncertainties in key parameter estimates from bioeconomic fisheries models, as well as highlighting the merits of including economics in MSE in general. The interaction between life history characteristics, fisheries variables and economic systems strongly affect the behaviour and robustness of the bioeconomic target RPs for the case studies fisheries. It was clear from these examples that the MSE approach has the potential to radically improve the robust estimation of bioeconomic RPs as well as the construction, evaluation, and implementation of economically-oriented harvest strategies.

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