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Abstract

Significant differences in liver copper content have been observed between rat inbred strains. To define loci controlling this trait, the offspring (n = 190) from an (LEW/OlaHsd × BC/CpbU) F₂-intercross was genetically analyzed. From each F₂ animal, liver copper content was determined and genomic DNA was screened with polymorphic DNA markers. We found a major quantitative trait locus (QTL) for liver copper content in females on chromosome 2 and in males on chromosome 10. Both QTLs accounted for approximately 20% of the genetic variance. In addition, suggestive linkage for liver copper content was found on rat chromosomes 1, 8, 10, 12, 14, and 19. The regions on these chromosomes contain genes that are responsible for 9.0–15.5% of the genetic variance of liver copper content.

Keywords

copper inbred strain liver QTL rat

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References

, Beems

, Joles

, Kaysen

, Beynen

. Iron and copper metabolism in analbuminaemic rats fed a high-iron diet. Comp Biochem Physiol 110A:131–138, 1995.

Hayashi

, Kuge

, Endoh

, Nakayama

, Arikawa

, Takazawa

, Okui

Hepatic copper accumulation induces DNA strand breaks in the liver cells of Long-Evans Cinnamon strain rats. Biochem Biophys Res Commun 276:174–178, 2000.

Schilsky

, Irani

, Gorla

, Volenberg

, Gupta

Biliary copper excretion capacity in intact animals: correlation between ATP7B function, hepatic mass, and biliary copper excretion. J Biochem Mol Toxicol 14:210–214, 2000.

De Wolf

, Fielmich-Bouman

, van Oost

, Beynen

, Křen

, Pravenec

, van Zutphen

LFM

, van Lith

. Genetic and correlation analysis of hepatic copper content in the rat. Biochem Biophys Res Commun 289:1247–1251, 2001.

Bottger

, den Bieman

, Lankhorst

, van Lith

, van Zutphen

LFM

. Strain-specific response to hypercholesterolaemic diets in the rat. Lab Anim 30:149–157, 1996.

Cockell

, Fischer

PWF

, Belonje

Elemental composition of anatomically distinct regions of rat liver. Biol Trace Elem Res 70:251–263, 1999.

Stam

, van Ooijen

. JoinMap™ Version 2.0: Software for the Calculation of Genetic Linkage Maps. Wageningen, The Netherlands: CPRO-DLO, 1995.

Petrie

, Watson

Statistics for Veterinary and Animal Science. London: Blackwell Science Ltd., 1999.

SPSS Inc. SPSS/PC⁺™ Version 4.0, Base Manual for the IBM PC/XTAT and PS/2V (Release 4.0). Chicago: SPSS Inc., 1990.

10.

Van Ooijen

, Maliepaard

MapQTL™ Version 3.0, Software for the Calculation of QTL Positions on Genetic Maps. Wageningen, The Netherlands: CPRO-DLO, 1996.

11.

Lander

, Botstein

Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121:185–199, 1989.

12.

Lander

, Kruglyak

Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11:241–247, 1995.

13.

Dracheva

, Remmers

, Chen

, Chang

, Gulko

, Kawahito

, Longman

, Wang

, Du

, Shepard

, Ge

, Joe

, Kotake

, Salstrom

, Furuya

, Hoffman

, Cannon

, Griffiths

, Wilder

. An integrated genetic linkage map with 1137 markers constructed from five F₂ crosses of autoimmune disease-prone and -resistant inbred rat strains. Genomics 63:202–226, 2000.

14.

Cox

. Disorders of copper transport. Br Med Bull 55:544–555, 1999.

15.

Szpirer

, Szpirer

, Levan

Report on rat chromosome 2. J Exp Anim Sci 40:19–26, 1999.

16.

Rosol

, Yarrington

, Latendresse

, Capen

. Adrenal gland: structure, function, and mechanisms of toxicity. Toxicol Pathol 29:41–48, 2001.

17.

Cousins

. Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin. Physiol Rev 65:238–309, 1985.

Quantitative Trait Loci Influencing Hepatic Copper in Rats

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