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

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

SN - 0962-8819

VL - 20

SP - 491

EP - 502

JO - Transgenic Research

JF - Transgenic Research

IS - 3

ER -