Assessing variable tarsal bone fusions in mice with Hoxa11 and Hoxd11 loss-of-function mutations
Location
Philadelphia, PA
Start Date
17-4-2026 1:30 PM
End Date
17-4-2026 2:30 PM
Description
INTRODUCTION: Hox genes are an important family of developmental patterning genes that play a key role in embryonic skeletal development. They are an important contributor to skeletal morphology throughout the body, and Hoxa11 and Hoxd11 are known to be expressed near the developing ankle. We have previously observed differences in calcaneus shape through 3D geometric morphometric analysis in mice with Hoxa11 and Hoxd11 loss-of-function mutations. During processing of micro-CT scans for the previous study, we also observed that variable fusion patterns existed between the other tarsal bones.
OBJECTIVES: The present study aims to assess whether variable fusion patterns observed in adult mouse tarsal bones differ between wild type mice and those with Hoxa11 and/or Hoxd11 loss-of-function mutations.
METHODS: We conducted a comparative morphological analysis of adult tarsal bones in wild type mice and mice with one, two, and three Hoxa11 and Hoxd11 loss-of-function alleles. Adult mouse limbs were micro-CT scanned at 5um resolution on a GE v|tome|x L 300. Scans were processed and visualized using Dragonfly ORS software. Tarsal morphology was evaluated through both gross 3D reconstructions and multi-planar, slice-by-slice cross-sectional analyses (n=70). The degree of fusion between the central tarsal bone and tarsal bone III (T3) was quantified using a 3-point ordinal grading scale: 1 (no fusion), 2 (partial fusion), 3 (complete fusion). Additional fusions between the central tarsal bone and tarsal bone II (T2) were also noted. Specimens were then grouped by Hoxa11 and Hoxd11 genotypes and analyzed with an Independent Samples Kruskal-Wallis test with Bonferroni corrected post-hoc pairwise comparisons in SPSS Version 28.
RESULTS: The majority of wild type specimens exhibit full fusion between the central tarsal and T3. This pattern is maintained in specimens with Hoxa11 loss-of-function mutations. Any number of Hoxd11 loss-of-function mutations, either alone or in combination with Hoxa11 loss-of-function mutations, increases the frequency of remaining unfused between the central tarsal and T3. Statistically significant differences are observed between wild type mice and mice that are homozygous for Hoxd11 loss-of-function mutations. Additional fusions between T2 and the central tarsal bone are present at low levels (16.7% of wild type), with increased prevalence in genotypes with any number of Hoxa11 loss-of-function mutations.
CONCLUSION: Changes in the types and frequency of tarsal fusions are observed in mice with Hoxa11 and Hoxd11 loss-of-function mutations. The most common change is loss of fusion between the central tarsal and T3 in mice with any number of Hoxd11 loss-of-function mutations. These data suggest a role for Hox11 genes in tarsal morphology and development of the intertarsal joints, with Hoxd11 having greater impacts to variable tarsal fusions.
Embargo Period
5-20-2026
Assessing variable tarsal bone fusions in mice with Hoxa11 and Hoxd11 loss-of-function mutations
Philadelphia, PA
INTRODUCTION: Hox genes are an important family of developmental patterning genes that play a key role in embryonic skeletal development. They are an important contributor to skeletal morphology throughout the body, and Hoxa11 and Hoxd11 are known to be expressed near the developing ankle. We have previously observed differences in calcaneus shape through 3D geometric morphometric analysis in mice with Hoxa11 and Hoxd11 loss-of-function mutations. During processing of micro-CT scans for the previous study, we also observed that variable fusion patterns existed between the other tarsal bones.
OBJECTIVES: The present study aims to assess whether variable fusion patterns observed in adult mouse tarsal bones differ between wild type mice and those with Hoxa11 and/or Hoxd11 loss-of-function mutations.
METHODS: We conducted a comparative morphological analysis of adult tarsal bones in wild type mice and mice with one, two, and three Hoxa11 and Hoxd11 loss-of-function alleles. Adult mouse limbs were micro-CT scanned at 5um resolution on a GE v|tome|x L 300. Scans were processed and visualized using Dragonfly ORS software. Tarsal morphology was evaluated through both gross 3D reconstructions and multi-planar, slice-by-slice cross-sectional analyses (n=70). The degree of fusion between the central tarsal bone and tarsal bone III (T3) was quantified using a 3-point ordinal grading scale: 1 (no fusion), 2 (partial fusion), 3 (complete fusion). Additional fusions between the central tarsal bone and tarsal bone II (T2) were also noted. Specimens were then grouped by Hoxa11 and Hoxd11 genotypes and analyzed with an Independent Samples Kruskal-Wallis test with Bonferroni corrected post-hoc pairwise comparisons in SPSS Version 28.
RESULTS: The majority of wild type specimens exhibit full fusion between the central tarsal and T3. This pattern is maintained in specimens with Hoxa11 loss-of-function mutations. Any number of Hoxd11 loss-of-function mutations, either alone or in combination with Hoxa11 loss-of-function mutations, increases the frequency of remaining unfused between the central tarsal and T3. Statistically significant differences are observed between wild type mice and mice that are homozygous for Hoxd11 loss-of-function mutations. Additional fusions between T2 and the central tarsal bone are present at low levels (16.7% of wild type), with increased prevalence in genotypes with any number of Hoxa11 loss-of-function mutations.
CONCLUSION: Changes in the types and frequency of tarsal fusions are observed in mice with Hoxa11 and Hoxd11 loss-of-function mutations. The most common change is loss of fusion between the central tarsal and T3 in mice with any number of Hoxd11 loss-of-function mutations. These data suggest a role for Hox11 genes in tarsal morphology and development of the intertarsal joints, with Hoxd11 having greater impacts to variable tarsal fusions.