Cytochrome b (5) null mouse: a new model for studying inherited skin disorders and the role of unsaturated fatty acids in normal homeostasis

Robert D. Finn, Lesley A. McLaughlin, Catherine Hughes, Chengli Song, Colin J. Henderson, C. Roland Wolf

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    Microsomal cytochrome b (5) is a ubiquitous, 15.2 kDa haemoprotein implicated in a number of cellular processes such as fatty acid desaturation, drug metabolism, steroid hormone biosynthesis and methaemoglobin reduction. As a consequence of these functions this protein has been considered essential for life. Most of the ascribed functions of cytochrome b (5), however, stem from in vitro studies and for this reason we have carried out a germline deletion of this enzyme. We have unexpectedly found that cytochrome b (5) null mice were viable and fertile, with pups being born at expected Mendelian ratios. However, a number of intriguing phenotypes were identified, including altered drug metabolism, methaemoglobinemia and disrupted steroid hormone homeostasis. In addition to these previously identified roles for this protein, cytochrome b (5) null mice displayed skin defects closely resembling those observed in autosomal recessive congenital ichthyosis and retardation of neonatal development, indicating that this protein, possibly as a consequence of its role in the de novo biosynthesis of unsaturated fatty acids, plays a central role in skin development and neonatal nutrition. Results from fatty acid profile analysis of several tissues suggest that cytochrome b (5) plays a role controlling saturated/unsaturated homeostasis. These data demonstrate that regional concentrations of unsaturated fatty acids are controlled by endogenous metabolic pathways and not by diet alone.

    Original languageEnglish
    Pages (from-to)491-502
    Number of pages12
    JournalTransgenic Research
    Volume20
    Issue number3
    DOIs
    Publication statusPublished - Jun 2011

    Keywords

    • Cytochrome b(5)
    • Ichthyosis
    • Methaemoglobinemia
    • Nutrition
    • Skin
    • Unsaturated fatty acids
    • CONGENITAL METHEMOGLOBINEMIA
    • ENDOPLASMIC-RETICULUM
    • LIPID-SYNTHESIS
    • MAMMARY-GLAND
    • B(5)
    • REDUCTASE
    • GENE
    • LACTATION
    • DESATURASE
    • PREGNANCY

    Cite this

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    title = "Cytochrome b (5) null mouse: a new model for studying inherited skin disorders and the role of unsaturated fatty acids in normal homeostasis",
    abstract = "Microsomal cytochrome b (5) is a ubiquitous, 15.2 kDa haemoprotein implicated in a number of cellular processes such as fatty acid desaturation, drug metabolism, steroid hormone biosynthesis and methaemoglobin reduction. As a consequence of these functions this protein has been considered essential for life. Most of the ascribed functions of cytochrome b (5), however, stem from in vitro studies and for this reason we have carried out a germline deletion of this enzyme. We have unexpectedly found that cytochrome b (5) null mice were viable and fertile, with pups being born at expected Mendelian ratios. However, a number of intriguing phenotypes were identified, including altered drug metabolism, methaemoglobinemia and disrupted steroid hormone homeostasis. In addition to these previously identified roles for this protein, cytochrome b (5) null mice displayed skin defects closely resembling those observed in autosomal recessive congenital ichthyosis and retardation of neonatal development, indicating that this protein, possibly as a consequence of its role in the de novo biosynthesis of unsaturated fatty acids, plays a central role in skin development and neonatal nutrition. Results from fatty acid profile analysis of several tissues suggest that cytochrome b (5) plays a role controlling saturated/unsaturated homeostasis. These data demonstrate that regional concentrations of unsaturated fatty acids are controlled by endogenous metabolic pathways and not by diet alone.",
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    author = "Finn, {Robert D.} and McLaughlin, {Lesley A.} and Catherine Hughes and Chengli Song and Henderson, {Colin J.} and Wolf, {C. Roland}",
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    Cytochrome b (5) null mouse: a new model for studying inherited skin disorders and the role of unsaturated fatty acids in normal homeostasis. / Finn, Robert D.; McLaughlin, Lesley A.; Hughes, Catherine; Song, Chengli; Henderson, Colin J.; Wolf, C. Roland.

    In: Transgenic Research, Vol. 20, No. 3, 06.2011, p. 491-502.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Cytochrome b (5) null mouse: a new model for studying inherited skin disorders and the role of unsaturated fatty acids in normal homeostasis

    AU - Finn, Robert D.

    AU - McLaughlin, Lesley A.

    AU - Hughes, Catherine

    AU - Song, Chengli

    AU - Henderson, Colin J.

    AU - Wolf, C. Roland

    PY - 2011/6

    Y1 - 2011/6

    N2 - Microsomal cytochrome b (5) is a ubiquitous, 15.2 kDa haemoprotein implicated in a number of cellular processes such as fatty acid desaturation, drug metabolism, steroid hormone biosynthesis and methaemoglobin reduction. As a consequence of these functions this protein has been considered essential for life. Most of the ascribed functions of cytochrome b (5), however, stem from in vitro studies and for this reason we have carried out a germline deletion of this enzyme. We have unexpectedly found that cytochrome b (5) null mice were viable and fertile, with pups being born at expected Mendelian ratios. However, a number of intriguing phenotypes were identified, including altered drug metabolism, methaemoglobinemia and disrupted steroid hormone homeostasis. In addition to these previously identified roles for this protein, cytochrome b (5) null mice displayed skin defects closely resembling those observed in autosomal recessive congenital ichthyosis and retardation of neonatal development, indicating that this protein, possibly as a consequence of its role in the de novo biosynthesis of unsaturated fatty acids, plays a central role in skin development and neonatal nutrition. Results from fatty acid profile analysis of several tissues suggest that cytochrome b (5) plays a role controlling saturated/unsaturated homeostasis. These data demonstrate that regional concentrations of unsaturated fatty acids are controlled by endogenous metabolic pathways and not by diet alone.

    AB - Microsomal cytochrome b (5) is a ubiquitous, 15.2 kDa haemoprotein implicated in a number of cellular processes such as fatty acid desaturation, drug metabolism, steroid hormone biosynthesis and methaemoglobin reduction. As a consequence of these functions this protein has been considered essential for life. Most of the ascribed functions of cytochrome b (5), however, stem from in vitro studies and for this reason we have carried out a germline deletion of this enzyme. We have unexpectedly found that cytochrome b (5) null mice were viable and fertile, with pups being born at expected Mendelian ratios. However, a number of intriguing phenotypes were identified, including altered drug metabolism, methaemoglobinemia and disrupted steroid hormone homeostasis. In addition to these previously identified roles for this protein, cytochrome b (5) null mice displayed skin defects closely resembling those observed in autosomal recessive congenital ichthyosis and retardation of neonatal development, indicating that this protein, possibly as a consequence of its role in the de novo biosynthesis of unsaturated fatty acids, plays a central role in skin development and neonatal nutrition. Results from fatty acid profile analysis of several tissues suggest that cytochrome b (5) plays a role controlling saturated/unsaturated homeostasis. These data demonstrate that regional concentrations of unsaturated fatty acids are controlled by endogenous metabolic pathways and not by diet alone.

    KW - Cytochrome b(5)

    KW - Ichthyosis

    KW - Methaemoglobinemia

    KW - Nutrition

    KW - Skin

    KW - Unsaturated fatty acids

    KW - CONGENITAL METHEMOGLOBINEMIA

    KW - ENDOPLASMIC-RETICULUM

    KW - LIPID-SYNTHESIS

    KW - MAMMARY-GLAND

    KW - B(5)

    KW - REDUCTASE

    KW - GENE

    KW - LACTATION

    KW - DESATURASE

    KW - PREGNANCY

    U2 - 10.1007/s11248-010-9426-1

    DO - 10.1007/s11248-010-9426-1

    M3 - Article

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    SP - 491

    EP - 502

    JO - Transgenic Research

    JF - Transgenic Research

    SN - 0962-8819

    IS - 3

    ER -