# Pudgy mouse rib deformities emanate from abnormal paravertebral longitudinal cartilage/bone accumulations

## TL;DR

A genetic mutation in the Dll3 gene causes severe rib and spine deformities in mice due to abnormal cartilage and bone accumulations.

## Contribution

The study identifies a dual mechanism involving the Dll3 gene mutation and altered tissue formation processes in rib malformation.

## Key findings

- Localized paravertebral cartilage/bone accumulations are linked to branched and fused ribs in pudgy mice.
- Rib and vertebral abnormalities occur asymmetrically in right and left sides of the mice.
- Deformation patterns vary between individual mice, suggesting multiple contributing factors.

## Abstract

The pudgy (pu/pu) mouse, caused by a recessive mutation in the Notch family Delta like-3 gene (Dll3), has severe rib, vertebral body and intervertebral disc abnormalities. Using whole-mount preparations and serial histologic sections we demonstrate: 1) localized paravertebral longitudinal cartilage/bone accumulations (PVLC/BAs) invariably associated with branched, fused and asymmetrically spaced ribs that emanate from it laterally; 2) abnormal rib formation immediately adjacent to abnormal vertebral body and intervertebral disc formation in asymmetric right/left fashion; and 3) patterns of rib deformation that differ in each mouse. Normal BALB/c embryo and age-matched non-affected pu/+ mice assessments allow for pu/pu comparisons. The Dll3 Notch family gene is involved in normal somitogenesis via the segmentation clock mechanism. Although pathogenesis of rib deformation is initially triggered by the Dll3 gene mutation, these findings of abnormal asymmetric costo-vertebral region structure imply that differing patterns cannot be attributed to this single gene mutation alone. All findings implicate a dual mechanism of malformation: the Dll3 gene mutation leading to subtle timing differences in traveling oscillation waves of the segmentation clock and further subsequent misdirection of tissue formation by altered chemical reaction-diffusion and epigenetic landscape responses. PVLC/BAs appear as primary supramolecular structures underlying severe rib malformation associated both with time-sensitive segmentation clock mutations and subsequent reactions.

Summary: Whole-mount preparations and serial histologic sections in pudgy (pu/pu) mice demonstrate localized paravertebral longitudinal cartilage/bone accumulations (PVLC/BAs) invariably associated with branched, fused and asymmetrically spaced ribs emanating laterally from them.