Publication Details

Novel loci regulating bone anabolic response to loading: expression QTL analysis in C57BL/6JXC3H/HeJ mice cross.

Authors:Kesavan C, Baylink DJ, Kapoor S, Mohan S
Title:Novel loci regulating bone anabolic response to loading: expression QTL analysis in C57BL/6JXC3H/HeJ mice cross.
Journal:Bone Aug 2007 , Vol 41 , pp. 223-30
Abstract:Variations in the expression levels of bone marker genes among the inbred strains of mice in response to mechanical loading (ML) are largely determined by genetic factors. To explore this, we performed four-point bending on tibiae of 10-week female F2 mice of B6XC3H cross using 9N at 2 Hz, 36 cycles, once per day for 12 days. We collected tibiae from these mice for RNA extraction. We then measured the expression changes of bone marker genes, bone sialoprotein (BSP), alkaline phosphatase (ALP) and housekeeping genes, beta-actin and peptidylprolyl isomerase A (PPIA), by using real-time PCR in both the loaded and the non-loaded tibiae of F2 mice (n=241). A genome-wide scan was performed using 111 micro satellite markers in DNA sample collected from these mice. Mean increase in gene expression, expressed as fold change, ranges from 2.8 to 3.0 for BSP and 2.7 to 2.8 for ALP. Both showed a skewed distribution with a heritability response of 87 to 91%. Absence of significant correlation between the increased gene expression vs. body weight (BW) and bone size (BS) suggests that bone response to loading is independent of BS or BW. Non-parametric mapping (MapQTL program 5) revealed that BSP and ALP expression in response to bending was regulated by several significant and suggestive QTL: Loci regulating both BSP and ALP were located on Chr 8 (60.1 cM), 16 (45.9 cM), 17 (14.2 cM), 18 (38.0 cM) and Chr 19 (3.3 cM); Loci specific to BSP were found on Chrs 1 (LOD score 10.4 at 91.8 cM), 5 (5.2 at 73.2 cM) and 9 (7.0 at 13.1 cM); Loci regulating only ALP were found on Chrs 1 (7.6 at 46 and 75.4 cM), 3 (8.3 at 47 cM) and 4 (5.6 at 54.6 cM). QTLs on Chrs 1, 3, 8, 9, 17 and 18 correspond to QTLs we previously reported by pQCT measurements, thus validating these findings. In addition, we found that the QTL associated with non-loaded tibiae for BSP and ALP on Chrs 4, 16 and 18 was identical to the QTLs associated with ML. This finding suggests that regions on these chromosomes are responsible for natural variation in expression of BSP and ALP as well as for ML. This is the first expression study to provide evidence for the presence of multiple genetic loci regulating bone anabolic response to loading in the B6XC3H intercross and will lead to a better understanding of how exercise improves the skeletal mass.   PUBMED: 17543594
Ontological Annotations:
  • D015211: Zellweger Syndrome (Publication, NCBO Annotator)
  • D032882: Comprehension (Publication, NCBO Annotator)
  • D019696: Peptidylprolyl Isomerase (Publication, NCBO Annotator)
  • D002875: Chromosomes (Publication, NCBO Annotator)
  • D001835: Body Weight (Publication, NCBO Annotator)
  • D051379: Mice (Publication, NCBO Annotator)
  • D000469: Alkaline Phosphatase (Publication, NCBO Annotator)
  • GO:0010467: gene expression (Publication, NCBO Annotator)
  • D006796: Housekeeping (Publication, NCBO Annotator)
  • D004247: DNA (Publication, NCBO Annotator)
  • D058574: Integrin-Binding Sialoprotein (Publication, NCBO Annotator)
  • D016133: Polymerase Chain Reaction (Publication, NCBO Annotator)
  • D020043: Genes, Essential (Publication, NCBO Annotator)
  • D056426: Genetic Loci (Publication, NCBO Annotator)
  • D007854: Lead (Publication, NCBO Annotator)
  • D000199: Actins (Publication, NCBO Annotator)
  • D001842: Bone and Bones (Publication, NCBO Annotator)
  • MA:0001459: bone (Publication, NCBO Annotator)
  • D012313: RNA (Publication, NCBO Annotator)
  • D015444: Exercise (Publication, NCBO Annotator)
  • D008815: Mice, Inbred Strains (Publication, NCBO Annotator)

13 GeneSets from this Publication:


Select gene sets below using the check boxes, and then add them to a project using the pull down below. You can also create a project using the pull down. To view a set, click on the GeneSetID:GeneSet Description shown in green below.
Expand Tier I Mouse 466 Genes GS135476: bone response to mechanical loading 1 (Brml1, Published QTL Chr 1)
Expand Tier I Mouse 758 Genes GS135477: bone response to mechanical loading 10 (Brml10, Published QTL Chr 4)
Expand Tier I Mouse 387 Genes GS135478: bone response to mechanical loading 11 (Brml11, Published QTL Chr 9)
Expand Tier I Mouse 440 Genes GS135479: bone response to mechanical loading 12 (Brml12, Published QTL Chr 19)
Expand Tier I Mouse 553 Genes GS135480: bone response to mechanical loading 13 (Brml13, Published QTL Chr 4)
Expand Tier I Mouse 538 Genes GS135481: bone response to mechanical loading 14 (Brml14, Published QTL Chr 2)
Expand Tier I Mouse 460 Genes GS135482: bone response to mechanical loading 2 (Brml2, Published QTL Chr 8)
Expand Tier I Mouse 238 Genes GS135484: bone response to mechanical loading 4 (Brml4, Published QTL Chr 3)
Expand Tier I Mouse 642 Genes GS135485: bone response to mechanical loading 5 (Brml5, Published QTL Chr 9)
Expand Tier I Mouse 269 Genes GS135486: bone response to mechanical loading 6 (Brml6, Published QTL Chr 17)
Expand Tier I Mouse 117 Genes GS135487: bone response to mechanical loading 7 (Brml7, Published QTL Chr 18)
Expand Tier I Mouse 398 Genes GS135488: bone response to mechanical loading 8 (Brml8, Published QTL Chr 1)
Expand Tier I Mouse 424 Genes GS135489: bone response to mechanical loading 9 (Brml9, Published QTL Chr 1)