Cytochrome b5 null mouse: a new model for studying inherited skin disorders and the role of unsaturated fatty acids in normal homeostasis.
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.
Finn
Robert D
RD
School of Applied Sciences, Ellison Building, Northumbria University, Newcastle, NE1 8ST, UK.
McLaughlin
Lesley A
LA
Hughes
Catherine
C
Song
Chengli
C
Henderson
Colin J
CJ
Roland Wolf
C
C
D000818:Animals; D015786:Cytochromes b5 / Q000235:genetics*; D004195:Disease Models, Animal; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D007057:Ichthyosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D012867:Skin / Q000473:pathology
D005231:Fatty Acids, Unsaturated; D015786:Cytochromes b5