Vps4b heterozygous mice do not develop tooth defects that replicate human dentin dysplasia I

Aiqin Hu,Jin Huang,Dan Guo,Fu Xiong,Danna Chen,Ting Lu,Yanjun Li,Weiwei Feng,Dong Chen,Xiangmin Xu

doi:10.1186/s12863-018-0699-3

Abstract

BackgroundVacuolar protein sorting-associated protein 4B (VPS4B) is a member of the ATP enzyme AAA protein family, and is mainly involved in protein degradation and cell membrane fusion. Recently, a dominant mutation in this gene was identified in human dentin dysplasia type I (DD-I). Herein, we report the generation of Vps4b knockout (Vps4b KO) mice; however, the homozygous Vps4b KO mutation was embryonic lethal at the early stages of embryo development, and we therefore report the results of heterozygous mutant mice.ResultsMice heterozygous for Vps4b did not develop tooth defects replicating human DD-I. Immunohistochemistry showed that gene KO was successful, as there was decreased expression of Vps4b in heterozygous mice; hematoxylin and eosin (H&E) staining also showed that the width of the pre-dentin zone was increased in heterozygous mice, although the arrangement of the odontoblasts was not significantly different from wild-type (WT) mice. However, H&E staining showed no obvious abnormalities in the bones of heterozygous mice. Moreover, stereomicroscopic and X-ray radiography results indicated no abnormal manifestations in teeth or bones. Furthermore, statistical analysis of the volume and density of dentin and enamel, as well as skeletal analysis, including the volume and separation of trabecular bone analyzed by micro-CT, all showed no differences between Vps4b heterozygotes and WT mice. In addition, there also were no significant differences in bone or cartilage mineralization as evaluated by Alcian blue–Alizarin red staining.ConclusionsThe heterozygous Vps4b KO mice do not develop tooth defects that replicate human DD-I and this is likely to be due to differences in tooth development between the two species. Consequently, further studies are needed to determine whether mice are an appropriate animal model for human tooth diseases.

Highlights

Vacuolar protein sorting-associated protein 4B (VPS4B) is a member of the ATP enzyme AAA protein family, and is mainly involved in protein degradation and cell membrane fusion
The gene encoding VPS4A is located on chromosome 16, while the gene encoding VPS4B is located on chromosome 18
(2019) 20:7 from our lab indicated that the VPS4B gene was one of the pathogenic genes associated with dentin dysplasia type I (DD-I), which regulates tooth development via interaction with Wnt/β-catenin canonical signaling [10]

Summary

Introduction

Vacuolar protein sorting-associated protein 4B (VPS4B) is a member of the ATP enzyme AAA protein family, and is mainly involved in protein degradation and cell membrane fusion. Vacuolar protein sorting 4 (VPS4) is one of the major members of the ATP enzyme AAA protein family and is known to promote protein degradation and cell membrane fusion [1,2,3]. Recent studies have found that VPS4B primarily participates in lysosomal degradation pathways, intracellular protein transport, viral body budding, and regulation of the different stages of cell division [8, 9]. A splicing mutation, IVS7 + 46C > G, genetically linked to DD-I in an extended Chinese family, was identified in VPS4B, and has been proven to cause DD-I in a loss-of-function manner. Our investigation of tooth development in zebrafish or in vitro revealed a function for the VPS4B gene in tooth development [10, 11]

Methods

Results

Conclusion