Genetically Humanized Animal Models

K. Samuelsson, N. Scheer, I. Wilson, C Wolf, Colin J Henderson

    Research output: Chapter in Book/Report/Conference proceedingChapter

    Abstract

    Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development.
    Original languageEnglish
    Title of host publicationComprehensive Medicinal Chemistry III
    EditorsSamuel Chackalamannil, David P. Rotella, Simon E. Ward
    PublisherElsevier
    Pages130-149
    Number of pages20
    ISBN (Electronic)9780128032015
    ISBN (Print)9780128032008
    DOIs
    Publication statusE-pub ahead of print - 13 Jun 2017

    Publication series

    NameReference Module in Chemistry, Molecular Sciences and Chemical Engineering
    PublisherElsevier

    Fingerprint

    Animal Models
    Drug-Related Side Effects and Adverse Reactions
    Drug Discovery
    Hepatocytes
    Pharmacokinetics
    Safety
    Liver
    Proteins

    Keywords

    • Chimeric liver-humanized mice
    • Drug distribution
    • Drug metabolism
    • Genetically humanized mice
    • Knockout mice
    • Toxicology

    Cite this

    Samuelsson, K., Scheer, N., Wilson, I., Wolf, C., & Henderson, C. J. (2017). Genetically Humanized Animal Models. In S. Chackalamannil, D. P. Rotella, & S. E. Ward (Eds.), Comprehensive Medicinal Chemistry III (pp. 130-149). (Reference Module in Chemistry, Molecular Sciences and Chemical Engineering). Elsevier. https://doi.org/10.1016/B978-0-12-409547-2.12376-5
    Samuelsson, K. ; Scheer, N. ; Wilson, I. ; Wolf, C ; Henderson, Colin J. / Genetically Humanized Animal Models. Comprehensive Medicinal Chemistry III. editor / Samuel Chackalamannil ; David P. Rotella ; Simon E. Ward. Elsevier, 2017. pp. 130-149 (Reference Module in Chemistry, Molecular Sciences and Chemical Engineering).
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    Samuelsson, K, Scheer, N, Wilson, I, Wolf, C & Henderson, CJ 2017, Genetically Humanized Animal Models. in S Chackalamannil, DP Rotella & SE Ward (eds), Comprehensive Medicinal Chemistry III. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering, Elsevier, pp. 130-149. https://doi.org/10.1016/B978-0-12-409547-2.12376-5

    Genetically Humanized Animal Models. / Samuelsson, K.; Scheer, N.; Wilson, I.; Wolf, C; Henderson, Colin J.

    Comprehensive Medicinal Chemistry III. ed. / Samuel Chackalamannil; David P. Rotella; Simon E. Ward. Elsevier, 2017. p. 130-149 (Reference Module in Chemistry, Molecular Sciences and Chemical Engineering).

    Research output: Chapter in Book/Report/Conference proceedingChapter

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    T1 - Genetically Humanized Animal Models

    AU - Samuelsson, K.

    AU - Scheer, N.

    AU - Wilson, I.

    AU - Wolf, C

    AU - Henderson, Colin J

    PY - 2017/6/13

    Y1 - 2017/6/13

    N2 - Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development.

    AB - Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development.

    KW - Chimeric liver-humanized mice

    KW - Drug distribution

    KW - Drug metabolism

    KW - Genetically humanized mice

    KW - Knockout mice

    KW - Toxicology

    U2 - 10.1016/B978-0-12-409547-2.12376-5

    DO - 10.1016/B978-0-12-409547-2.12376-5

    M3 - Chapter

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    T3 - Reference Module in Chemistry, Molecular Sciences and Chemical Engineering

    SP - 130

    EP - 149

    BT - Comprehensive Medicinal Chemistry III

    A2 - Chackalamannil, Samuel

    A2 - Rotella, David P.

    A2 - Ward, Simon E.

    PB - Elsevier

    ER -

    Samuelsson K, Scheer N, Wilson I, Wolf C, Henderson CJ. Genetically Humanized Animal Models. In Chackalamannil S, Rotella DP, Ward SE, editors, Comprehensive Medicinal Chemistry III. Elsevier. 2017. p. 130-149. (Reference Module in Chemistry, Molecular Sciences and Chemical Engineering). https://doi.org/10.1016/B978-0-12-409547-2.12376-5