A Study on Variations of HDL Levels in Female vs. Male Mice

The Battle of the Sexes:

Presented by:Sean Roney

Teresa LeslieCourtney Deshayes

• QTL- Quantitative Trait Locus

• 2+ strains, phenotypic data vs. genotypic data

• Summarizes action, interaction, number, and precise location of regions

• Can compare with knockout and over expression

What in the World is QTL-

HDL vs. LDL

HDL- helps prevent

cardiovascular disease

Cardiovascular disease-

hardening of the arteries

The Basic Background-

• Same environment, variation in plasma lipoprotein concentration– Genetic Background

• Nutrition, “safe” high-fat diet– Similar to humans

• Male vs. Female– Is sex a factor? – Compared two studies

Experimental Factors-

Actual Experiment-• Two Studies– 330 male R111x129– 294 female B6x129

• Length – 12 weeks (male) and 14 weeks (female)

• Plasma lipoprotein levels (HDL) in mice

Initial HDL Levels-Sex: n Plasma HDL mg/dl

Female 294 81 +/- 1

Male 330 143 +/- 2

•Males higher HDL levels, testosterone -- Difference of about 62 mg/dl

•Comparison- human females higher than males

Male QTLs ↑

Female QTLs ↓

QTL Analysis-

Table of Data-

Sex: # Sig QTLs

Hdlq5 Hdlq14 Hdlq15 Hdlq16 Hdlq17 Hdlq18 Hdlq19

Male 3 X X X

Female 6 X X X X X X

• LOD scores range from 2.6-9.8

• Only HDL QTLs compared

Results-• Male- Hdlq5 candidate gene APOA2

• Female- Hdlq15 (interacts with Hdlq 14 and 19) APOA2

• Information relatable to humans

• Confirmed with knockout and over expression methods

Other Findings-• Female- – Hdlq18 is novel– Hdlq16 leads to gene involved with lipoprotein

metabolism

• Both-– Hdlq17 APOA1/APOC3/APOA4– Male outside the 95% CI

Conclusion-• Males and females have some

comparable data

• Females have several QTLs that males do not, investigate further

• Information is relatable to humans

References-• Malcolm A. Lyons, Ron Korstanje, Renhua Li, Kenneth A. Walsh, Gary A. Churchill, Martin C.

Carey, and Beverly Paigen. “Genetic contributors to lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and RIIIS/J inbred mice.” Physiol Genomics 17:114-121, 2004. First published Feb 10, 2004.

• Ishimori, Naoki, Renhua Li, Peter M. Kelmenson, Ron Korstanje, Kenneth A. Walsh, Gary A. Churchill, Kristina Forsman-Semb, and Beverly Paigen. "Quantitative Trait Loci Analysis for Plasma HDL-Cholesterol Concentrations and Atherosclerosis Susceptibility Between Inbred Mouse Strains C57BL/6J and 129S1/SvImJ." Arteriosclerosis, Thrombosis, and Vascular Biology 24 (2003): 161-66.

• Miles, C. & Wayne, M. (2008) Quantitative trait locus (QTL) analysis. Nature Education 1(1)

• Some homology data for this paper were retrieved from the Mouse Genome Database (MGD), Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, Maine. World Wide Web (URL: http://www.informatics.jax.org). (June 9, 2010)

A Monumental Thanks to-• Randy Von Smith, PhD

• Tobias Beckwith

• Brook Milligan, PhD

• Jackson Laboratories

• NIH- RISE Program