CALL FOR PAPERS Computational Modeling of Physiological Systems Epistasis contributes to the genetic buffering of plasma HDL cholesterol in mice

نویسندگان

  • Renhua H. Li
  • Gary A. Churchill
چکیده

Li RH, Churchill GA. Epistasis contributes to the genetic buffering of plasma HDL cholesterol in mice. Physiol Genomics 42A: 228 –234, 2010. First published September 21, 2010; doi:10.1152/physiolgenomics.00044.2010.—Stressful environmental factors, such as a high-fat diet, can induce responses in the expression of genes that act to maintain physiological homeostasis. We observed variation in plasma concentrations of high-density lipoprotein (HDL) cholesterol across inbred mouse strains in response to high dietary fat intake. Several strains, including C57BL/6J, have stable levels of plasma HDL independent of diet, whereas other strains, including DBA2/J, show marked changes in plasma HDL. To explore this phenomenon further, we used publicly available data from a C57BL/6J DBA/2J intercross to identify genetic factors that associate with HDL under high-fat diet conditions. Our analysis identified an epistatic interaction that plays a role in the buffering of HDL levels in C57BL/6J mice, and we have identified Arl4d as a candidate gene that mediates this effect. Structural modeling further elucidates the interaction of genetic factors that contribute to the robustness of HDL in response to high-fat diet in the C57BL/6J strain.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Epistasis contributes to the genetic buffering of plasma HDL cholesterol in mice.

Stressful environmental factors, such as a high-fat diet, can induce responses in the expression of genes that act to maintain physiological homeostasis. We observed variation in plasma concentrations of high-density lipoprotein (HDL) cholesterol across inbred mouse strains in response to high dietary fat intake. Several strains, including C57BL/6J, have stable levels of plasma HDL independent ...

متن کامل

Intestinal ABCA1 directly contributes to HDL biogenesis in vivo.

Plasma HDL cholesterol levels are inversely related to risk for atherosclerosis. The ATP-binding cassette, subfamily A, member 1 (ABCA1) mediates the rate-controlling step in HDL particle formation, the assembly of free cholesterol and phospholipids with apoA-I. ABCA1 is expressed in many tissues; however, the physiological functions of ABCA1 in specific tissues and organs are still elusive. Th...

متن کامل

ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease.

Blood high-density lipoprotein (HDL) levels are inversely related to risk for cardiovascular disease, implying that factors associated with HDL metabolism are atheroprotective. One of these factors is ATP-binding cassette transporter A1 (ABCA1), a cell membrane protein that mediates the transport of cholesterol, phospholipids, and other metabolites from cells to lipid-depleted HDL apolipoprotei...

متن کامل

Genetic analysis of agronomic and physiological traits of bread wheat (Triticum aestivum L.) using generation mean analysis under drought stress conditions and spring planting in the cold climate

Study of heritability and gene action to improve agronomic and physiological traits, especially under drought stress conditions, are very important. The objectives of this study were to investigate heritability for important agronomic traits and some physiological characters in a cross between two spring wheat cultivars. The experiment was carried out using different generations (BC1, BC2, F3, ...

متن کامل

Transgenic Expression of Cholesterol-7- -Hydroxylase Prevents Atherosclerosis in C57BL/6J Mice

C57BL/6J mice are susceptible to atherosclerosis when fed a diet consisting of fat, cholesterol, and taurocholate. The susceptibility to diet-induced atherosclerosis is linked to a reduction in plasma high density lipoprotein (HDL). Diet-induced reduction of plasma HDL shows a physiological and a genetic correlation with repression of cholesterol-7-hydroxylase, the liver-specific enzyme that re...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2010