Related Experiment Video

Updated: Jun 14, 2025

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
08:42

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

4.4K

Functional analysis of a novel pathogenic variant in CREBBP associated with bone development

Qing Fang1, Yunlan Xu2, Jue Feng2

  • 1Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, P. R. China.

Pediatric Research
|August 31, 2024
PubMed

Insights

A novel CREBBP variant (p.R1289W) impairs skeletal development in mice, causing reduced body length and altered bone cell function. This finding highlights CREBBP's role in non-syndromic skeletal dysplasia.

Area of Science:

  • Genetics and Molecular Biology
  • Developmental Biology
  • Orthopedics

Background:

  • CREBBP is implicated in syndromic skeletal dysplasias, but its role in non-syndromic bone development is less understood.
  • A novel pathogenic CREBBP variant (c.C3862T/p.R1288W) was identified in a patient with non-syndromic polydactyly.
  • This study investigates the skeletal impact of this specific CREBBP variant.

Purpose of the Study:

  • To create and characterize a mouse model for a novel pathogenic CREBBP variant (p.R1289W).
  • To elucidate the molecular mechanisms by which this CREBBP variant affects bone development.
  • To determine if this variant can cause non-syndromic skeletal dysplasia.

Main Methods:

  • Generated a homozygous Crebbp p.R1289W mouse model.
  • Compared skeletal phenotypes of mutant and wild-type (WT) mice.
  • Isolated and analyzed bone marrow stem cells (BMSCs) for proliferation, apoptosis, and differentiation potential.

Main Results:

  • Crebbp p.R1289W mice exhibited significantly reduced body length and increased digit cartilage length.
  • BMSCs from mutant mice showed decreased proliferation and increased apoptosis.
  • Analysis of the distal femoral growth plate revealed reduced proliferation and elevated apoptosis in Crebbp p.R1289W mice.
  • Evidence suggests Crebbp p.R1289W promotes chondrocyte differentiation.

Conclusions:

  • The Crebbp p.R1289W variant plays a pathogenic role in mouse skeletal development.
  • This variant can independently cause non-syndromic skeletal dysplasia.
  • The study provides the first animal model for this novel CREBBP variant, advancing understanding of its skeletal disease mechanisms.
Abstract

More Related Videos

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

9.7K
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila00:06

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

13.6K

Related Concept Videos

Bone Formation by Endochondral Ossification01:24

Bone Formation by Endochondral Ossification

Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
4.1K
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
38.2K
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
2.8K
Compact Bone01:27

Compact Bone

Most bones contain compact and spongy osseous tissue, but their distribution and concentration vary based on the bone's overall function.
Compact bone, also called cortical bone, is the denser, stronger of the two types of bone tissue. It is found under the periosteum and in the diaphyses of long bones, where it provides support and protection. The microscopic structural unit of compact bone is called an osteon, or haversian system. Each osteon is composed of concentric rings of calcified...
11.3K
Bone Formation by Intramembranous Ossification01:29

Bone Formation by Intramembranous Ossification

Intramembranous ossification is one of the two processes involved in the development of bones within an embryo. The flat bones of the face, most of the cranial bones, and the clavicles are formed via this process. During intramembranous ossification, the bones develop directly from sheets of undifferentiated mesenchymal connective tissue.
The process begins when mesenchymal cells in the embryonic skeleton gather together and differentiate into osteogenic cells, which then develop into ...
5.7K
Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
196