DOI: 10.5061/dryad.7h44j1032
title: Data from: Sex specific emergence of trisomic Dyrk1a-related skeletal phenotypes in the development of a Down syndrome mouse model

description: 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.
description: 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/cm<sup>3</sup> 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).
description: # 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