Data from: Sex specific emergence of trisomic Dyrk1a-related skeletal phenotypes in the development of a Down syndrome mouse model
Data files
Sep 03, 2024 version files 86.85 KB
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README.md
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ts65dn_cx4945_treatment_p30.csv
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ts65dn_dyrk1a_conditional_normalization_p30.csv
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ts65dn_dyrk1a_germline_normalization_p30-p36.csv
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ts65dn_p12-p42.csv
Abstract
Skeletal insufficiency affects all individuals with Down syndrome (DS) or Trisomy 21 (Ts21) and may alter bone strength throughout development due to a reduced period of bone formation and early attainment of peak bone mass compared to typically developing individuals. Appendicular skeletal deficits also appear in males before females with DS. In femurs of male Ts65Dn DS model mice, cortical deficits were pronounced throughout development, but trabecular deficits and Dyrk1a overexpression were transitory until postnatal day (P) 30 when there were persistent trabecular and cortical deficits and Dyrk1a was trending overexpression. Correction of DS-related skeletal deficits by a purported DYRK1A inhibitor or through genetic means beginning at P21 was not effective at P30, but germline normalization of Dyrk1a improved male bone structure by P36. Trabecular and cortical deficits in female Ts65Dn mice were evident at P30 but subsided by P36, typifying periodic developmental skeletal normalizations that progressed to more prominent bone deficiencies. Sex-dependent differences in skeletal deficits with a delayed impact of trisomic Dyrk1a are important to find temporally specific treatment periods for bone and other phenotypes associated with Ts21.
README: Sex-specific emergence of trisomic Dyrk1a-related skeletal phenotypes in the development of a Down syndrome mouse model
These data were utilized in the following manuscript: LaCombe, J.M. et al. 2024 Disease Models and Mechanisms
male_ts65dn_p12-p42 contains all body weight, femur length, and micro-computed tomography data reported for male Ts65Dn mice
at P12, P15, P18, P24, P27, P30, and P42.
Columns are as follows:
Animal ID
Age of animal at dissection in postnatal days where P0 is the day of birth
Sex where M = male
Genotype
Trabecular bone mineral density (BMD) in g/cm^3
Trabecular bone volume fraction (BV/TV) in %
Trabecular thickness (Tb.Th) in mm
Trabecular separation (Tb.Sp) in mm
Trabecular number (Tb.N) in 1/mm
Total cortical cross-sectional area (Tt.Ar) in mm^2
Marrow area (Ma.Ar) in mm^2
Cortical bone area (Ct.Ar) in mm^2
Cortical bone thickness (Ct.Th) in mm
Periosteal bone perimeter (Ps.Pm) in mm
Endocortical bone perimeter (Ec.Pm) in mm
Maximum moment of inertia (Imax) in mm^4
Minimm moment of inertia (Imin) in mm^4
Inertia about the anterior-posterior axis (Iap) in mm^4
Inertia about the medial-lateral axis (Iml) in mm^4
Section modulus (Sec.Mod) in mm^3
Cortical tissue mineral density (TMD) in hydroxyaptite(HA)g/cm^3
Body weight immediately following terminal dosage of isoflurane in g
ts65dn_dyrk1a_germline_normalization_p30-p36 contains body weight, femur length, and micro-computed tomography data reported for male and female Ts65Dn x Dyrk1a+/- offspring
at P30 and P36.
Columns are as follows:
Animal ID
Age of animal at dissection in postnatal days where P0 is the day of birth (note: there are 7 instances were animals were P35 or P37 at dissection, these were grouped with the P36 animals)
Sex where M = male and F = female
Genotype
Trabecular bone mineral density (BMD) in g/cm^3
Trabecular bone volume fraction (BV/TV) in %
Trabecular thickness (Tb.Th) in mm
Trabecular separation (Tb.Sp) in mm
Trabecular number (Tb.N) in 1/mm
Total cortical cross-sectional area (Tt.Ar) in mm^2
Marrow area (Ma.Ar) in mm^2
Cortical bone area (Ct.Ar) in mm^2
Cortical bone thickness (Ct.Th) in mm
Periosteal bone perimeter (Ps.Pm) in mm
Endocortical bone perimeter (Ec.Pm) in mm
Maximum moment of inertia (Imax) in mm^4
Minimm moment of inertia (Imin) in mm^4
Inertia about the anterior-posterior axis (Iap) in mm^4
Inertia about the medial-lateral axis (Iml) in mm^4
Section modulus (Sec.Mod) in mm^3
Cortical tissue mineral density (TMD) in hydroxyaptite(HA)g/cm^3
Body weight immediately following terminal dosage of isoflurane in g
ts65dn_dyrk1a_conditional_normalization_p30 contains body weight, femur length, and femoral micro-computed tomography data of reported for P30 male Ts65Dn mice fed doxycycline at postnatal day 21 to
inactivate Dyrk1a via a TET-on system.
Columns are as follows:
Animal ID
Age of animal at dissection in postnatal days where P0 is the day of birth
Sex where M = male
Genotype
Trabecular bone mineral density (BMD) in g/cm^3
Trabecular bone volume fraction (BV/TV) in %
Trabecular thickness (Tb.Th) in mm
Trabecular separation (Tb.Sp) in mm
Trabecular number (Tb.N) in 1/mm
Total cortical cross-sectional area (Tt.Ar) in mm^2
Marrow area (Ma.Ar) in mm^2
Cortical bone area (Ct.Ar) in mm^2
Cortical bone thickness (Ct.Th) in mm
Periosteal bone perimeter (Ps.Pm) in mm
Endocortical bone perimeter (Ec.Pm) in mm
Maximum moment of inertia (Imax) in mm^4
Minimm moment of inertia (Imin) in mm^4
Inertia about the anterior-posterior axis (Iap) in mm^4
Inertia about the medial-lateral axis (Iml) in mm^4
Section modulus (Sec.Mod) in mm^3
Cortical tissue mineral density (TMD) in hydroxyaptite(HA)g/cm^3
Body weight immediately following terminal dosage of isoflurane in g
ts65dn_cx4945_treatment_p30 contains femur length and femoral micro-computed tomography data at P30 and body weight from P21 until P30 for male Ts65Dn animals treated with vehicle (10%DMSO:90%PBS) or
75mg/kg/day CX-4945 by oral gavage from P21 until P29.
Columns are as follows:
Animal ID
Age of animal at dissection in postnatal days where P0 is the day of birth
Sex where M = male
Genotype
Treatment
Trabecular bone mineral density (BMD) in g/cm^3
Trabecular bone volume fraction (BV/TV) in %
Trabecular thickness (Tb.Th) in mm
Trabecular separation (Tb.Sp) in mm
Trabecular number (Tb.N) in 1/mm
Total cortical cross-sectional area (Tt.Ar) in mm^2
Marrow area (Ma.Ar) in mm^2
Cortical bone area (Ct.Ar) in mm^2
Cortical bone thickness (Ct.Th) in mm
Periosteal bone perimeter (Ps.Pm) in mm
Endocortical bone perimeter (Ec.Pm) in mm
Maximum moment of inertia (Imax) in mm^4
Minimm moment of inertia (Imin) in mm^4
Inertia about the anterior-posterior axis (Iap) in mm^4
Inertia about the medial-lateral axis (Iml) in mm^4
Section modulus (Sec.Mod) in mm^3
Cortical tissue mineral density (TMD) in hydroxyaptite(HA)g/cm^3
Live body weight before treatment at P21 in g
Live body weight before treatment at P22 in g
Live body weight before treatment at P23 in g
Live body weight before treatment at P24 in g
Live body weight before treatment at P25 in g
Live body weight before treatment at P26 in g
Live body weight before treatment at P27 in g
Live body weight before treatment at P28 in g
Live body weight before treatment at P29 in g
Live body weight before dissection at P30 in g
Average live body weight in g
Change in body weight (live body weight at P21 subtracted from live body weight at P30) in g
Methods
Scans and analysis were performed on right femurs as described (Sloan et al., 2023) using a SkyScan 1172 high-resolution μCT system (Bruker, Kontich, Belgium). Flat field corrections occurred prior to scanning. Hydroxyapatite phantoms (0.25 and 0.75g/cm3 CaHA) were scanned once per week of scanning. Scanning parameters are as follows: 60kV, 12µm resolution, 885ms integration time, 0.7° angular increment, frame averaging of 4. The entire length of the femurs from P12, P15, P18, P24, and P27 were scanned, but due to size constraints, samples from P30 and P42 were scanned from the distal condyles of the femur to at least the third trochanter. Trabecular microarchitecture was analyzed by identifying a trabecular region of interest (ROI) beginning at the proximal end of the distal growth plate and extending proximally based on 10% of the bone length from the proximal end of the distal growth plate to the widest region of the third trochanter using SkyScan CT Analyzer (CTAn) and a custom MATLAB code to exclude the outer cortical bone, using lower greyscale threshold of 45 (P12 mice) or 55 (all other ages) and upper greyscale threshold of 255, as described in previous publications (Goodlett et al., 2020, Stringer et al., 2017a, Thomas et al., 2020, Sloan et al., 2023). The cortical ROI was defined as a region of seven transverse slices at 60% of the overall length of the bone from the proximal end of the distal growth plate and cortical geometry was measured as previously described using MATLAB (Goodlett et al., 2020, Stringer et al., 2017a, Thomas et al., 2020, Sloan et al., 2023).