Figure 1.

Mice lacking PTHrP-(67–137) (Δ/Δ) have impaired growth rate, increased mortality, and gross morphological abnormalities. A) Growth rate in Δ/Δ mice was significantly stunted when compared to control mice (+/+, +/Δ), with no differences between +/+ and +/Δ animals. B) Cumulative mortality rate for Δ/Δ pups was 35% by d 2 and 95% by d 10. C) Δ/Δ mice had a chondrodysplastic phenotype that was present as early as d E18.5 of gestation (i, white arrow), at birth (ii), but was clearly evident at d 3 postpartum (iii). Dwarfism and kyphosis were apparent in pups older than 3 d (iii–v). Craniofacial dysplasia with foreshortening was present as early as E18.5 (i, black arrow). D) Skeletal staining of 3-d-old Δ/Δ mice revealed less calvarial and rib mineralization (black arrows), and chondrodysplasia (white arrows). E) Micro-CT images of 15-d-old mice confirmed cranial dysplasia, spherical skulls, rostrocaudal facial shortening, kyphosis, and chondrodysplasia. F) Gross craniofacial morphology of 2- to 12-d-old Δ/Δ pups revealed a spherical skull with rostral foreshortening, tongue protrusion (black arrows), and delayed dental eruption with malaligned incisors that had a chalky discoloration (white arrow). G) On micro-CT, lateral, coronal, and rostral views showed morphological differences between Δ/Δ and control skulls (i–iv). There were differences in dental structure. Notice the proximity of the tympanic ring (white arrow) to the third molar in the Δ/Δ skull (iii), confirming foreshortening of the maxillae and mandible.