title: Congenic Strains Confirm the Pleiotropic Effect of Chromosome 4 QTL on Mouse Femoral Geometry and Biomechanical Performance.
abstract: A pleiotropic quantitative trait locus (QTL) for bone geometry and mechanical performance in mice was mapped to distal chromosome 4 via an intercross of recombinant congenic mice HcB-8 and HcB-23. To study the QTL in isolation, we have generated C3H.B10-(rs6355453-rs13478087) (C.B.4.3) and C3H.B10-(rs6369860-D4Mit170) (C.B.4.2) congenic strains that harbor ~20 Mb and ~3 Mb, respectively, of chromosome 4 overlapping segments from C57BL/10ScSnA (B10) within the locus on a C3H/DiSnA (C3H) background. Using 3-point bend testing and standard beam equations, we phenotyped these mice for femoral mid-diaphyseal geometry and biomechanical performance. We analyzed the results via 2-way ANOVA, using sex and genotype as factors. In the C.B.4.3 strain, we found that homozygous B10/B10 male mice had smaller cross sectional area (CSA) and reduced total displacement than homozygous C3H/C3H mice. Sex by genotype interaction was also observed for maximum load and stiffness for C3H/C3H and B10/B10 mice, respectively. In C.B.4.2 strain, we found that homozygous B10/B10 mice had lower total displacement, post-yield displacement (PYD), stiffness, yield load and maximum load than mice harboring C3H allele. Sex by genotype interaction was observed in B10/B10 mice for perimeter, outer minor axis (OMA) and CSA. There were no significant differences in tissue level mechanical performance, which suggest that the QTL acts primarily on circumferential bone size. These data confirm the prior QTL mapping data and support other work demonstrating the importance of chromosome 4 QTL on bone modeling and bone responses to mechanical loading.
authors: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors: Jasmin
authors: J
authors: Kristianto
authors: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors: Suzanne J
authors: SJ
authors: Litscher
authors: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors: Michael G
authors: MG
authors: Johnson
authors: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors: Forum
authors: F
authors: Patel
authors: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors: Mital
authors: M
authors: Patel
authors: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors: Jacqueline
authors: J
authors: Fisher
authors: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors: Ryley K
authors: RK
authors: Zastrow
authors: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors: Abigail B
authors: AB
authors: Radcliff
authors: Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.|William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, United States of America.|Milwaukee VA Medical Center, Milwaukee, Wisconsin, United States of America.
authors: Robert D
authors: RD
authors: Blank
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000235:genetics; D033481:Chromosomes, Mammalian; D005260:Female; D005269:Femur / Q000033:anatomy & histology* / Q000502:physiology*; D008297:Male; D020297:Mice, Congenic; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D040641:Quantitative Trait Loci