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Quantitative trait loci for steady-state platelet count in mice

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Abstract

Platelet count in humans is a strongly genetically regulated trait, with approximately 85% of the interindividual variance in platelet numbers attributable to genetic factors. Inbred mouse strains also have strain-specific platelet count ranges. As part of a project to identify novel factors that regulate platelet count, we identified two inbred mouse strains, CBA/CaH and QSi5, with substantial differences in platelet count (mean values of 581 vs. 1062 × 109/L). An F2 intercross resource of 1126 animals was bred from these two parental strains for a genomewide scan for quantitative trait loci (QTL) for platelet count. QTL were identified on MMU1 (LOD 6.8, p < 0.0005) and MMU11 (LOD 11.2, p < 0.0005) by selectively genotyping animals from the extremes of the F2 platelet count distribution. Three other QTL of suggestive statistical significance were also detected on MMU7, 13, and 17. It is noteworthy that no QTL were detected in the vicinity of the genes encoding thrombopoietin (Thpo), and its receptor (c-Mpl), both known to influence platelet production. Comparison of gene expression levels between the parental mouse strains by microarrays also showed little difference in the mRNA levels of these known candidate genes. These results represent the first published use of a genetic linkage-based approach in a mouse model toward the identification of genetic factors that regulate platelet count.

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Acknowledgments

The authors acknowledge with gratitude the support of Professor Colin Chesterman, the Haematology Department, and the Molecular & Cytogenetics Unit of South Eastern Area Laboratory Services, Sydney. We would like to thank Dr. Alan Baxter of the Centenary Institute, Sydney, for providing microsatellite markers, Dr. Zbigniew Rudzki and staff at Medvet Science in IMVS, Adelaide, South Australia, for genotyping the samples, and the staff at The Clive and Vera Ramaciotti Centre for Gene Function Analysis at UNSW for technical support with the microarray work. CC holds a Medical Postgraduate Award of the National Health and Medical Research Council of Australia. The Centre for Vascular Research is supported by a Research Development Infrastructure Grant from the NSW Department of Health and a Program Grant from the National Health and Medical Research Council of Australia. This project received support from the University of New South Wales University Research Support Program, a University of Sydney Sesqui R & D grant, and a Macquarie University research grant.

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Correspondence to Michael F. Buckley.

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Cheung, C.C., Martin, I.C., Zenger, K.R. et al. Quantitative trait loci for steady-state platelet count in mice. Mamm Genome 15, 784–797 (2004). https://doi.org/10.1007/s00335-004-2408-y

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