Table III.
Key pathological and quantitative measures of disease severity in various knock-in mouse models of PSACH-MED and novel ER stress phenocopies.
| Model | Age at onset | Final reduction in bone length
|
Cell proliferation
|
Apoptosis
|
Protein retention | ER stress | Stress pathway | ||
|---|---|---|---|---|---|---|---|---|---|
| 3 weeks | 6 weeks | 9 weeks | 3 weeks | 3 weeks | |||||
| Comp D469del | ~6 weeks | No differences | ↓ 6% | ↓ 5% | ↓ 17% | ↑ 90-fold (Pz) ↑ 5-fold (Hz) |
Yes | Yes | Novel (APR/EOR) |
| Comp T585M | ~9 weeks | No differences | No differences | ↓ 5% | ↓ 24% | ↑ 3-fold (Rz) ↑ 12-fold (Pz) ↑ 3-fold (Hz) |
Slight | Mild | Mild UPR |
| Matn3 V194D | ~2 weeks | ↓ 12% | ↓ 13% | ↓ 12% | ↑ 16% | Spatially dysregulated | Yes | Yes | UPR |
| Col2-TgRdw | At birth | ↓ 8% | ↓ 5% | ↓ 5% | ↑ 21% | No differences | Yes | Yes | UPR |
| Col2-Tgcog | ~3 weeks | ↓ 7% | ↓ 4% | ↓ 4% | ↑ 12% | No differences | Yes | Yes | Novel |
EOR, ER overload response; ER, endoplasmic reticulum; APR, aggregated protein response; UPR, unfolded protein response; Pz, proliferative zone; Hz, hypertrophic zone; Rz, resting zone; PSACH, pseudoachondroplasia; MED, multiple epiphyseal dysplasia.