Lrp4KI Mice Have a High Bone Mass Phenotype
(A and B) (A) Whole-body bone mineral density (BMD) was significantly elevated in female Lrp4KI mice versus WT (+/+) and heterozygous (+/KI) littermates, despite (B) normal body mass.
(C–G) (D–G) Trabecular bone volume fraction (Tb.BV/TV) in the distal femur and fifth lumbar vertebra (L5) and cortical thickness (Ct.Th) in the mid-diaphyseal femur were significantly increased in 18-week-old female Lrp4KI mice compared with WT (+/+) and heterozygous (+/KI) littermates, despite (C) normal femur length. (E) The center panel depicts μCT reconstructions from the midshaft femur (upper), distal femur (middle) and vertebral body (lower) from representative +/+, +/KI, and KI/KI mice. Scale bar, 1 mm.
(H–J) Peripheral quantitative computed tomography (pQCT) measurements through the proximal tibia of 8-week-old female +/+, +/KI, and KI/KI mice reveal an increase in trabecular BMD and cortical BMC among KI/KI mice.
(K–M) Mechanical testing of femora from 18-week-old female +/+, +/KI, and KI/KI mice reveal increased ultimate force and energy to ultimate force (FU) among knockin mice.
(N–P) Parietal thickness and planar area of foramen ovale in 18-week-old female +/+ and KI/KI female crania were not affected by the mutation. Male data are presented in Table S2. For (A) and (B), *p < 0.05 for comparison to +/+ by repeated measures ANOVA; for (C)–(P), *p < 0.05 for comparison to +/+ mice, using one-way ANOVA followed by Fisher's protected least significant differences (PLSD) post hoc tests. n = 10/group. Data are presented as means ±SEM.
See also Figure S1, Tables S1 and S2.