Histological Analysis of Dentinogenesis Imperfecta in Slc39a13/Zip13 Knockout Mice

Abstract

This study focused on the abnormality of dentin matrix to clarify the pathogenesis of human dentinogenesis imperfecta (DI). Dentin matrix of mandibular molars from wild type (Zip13+/+) and Slc39a/ Zip13 knockout (KO) mice were examined histologically. Hematoxylin and eosin, as well as silver staining, were used for light microscopy. Samples were also observed under backscattered and transmission electron microscopy. Immunohistochemistry using type I collagen was also carried out. Results showed that Zip13-KO mice exhibited 1) lamellated dentin matrix with accentuated incremental lines under the light microscope, 2) abnormal collagen fibers and round shape collagen molecules in transmission electron microscope, and 3) unusual immunoreaction to collagen type I. The similarity in the histological features of dentin in Zip13-KO mice to human DI indicates that Zip13-KO mice may be used as models for investigating the mechanism of human DI.

Molecular pathogenesis of Spondylocheirodysplastic Ehlers‐Danlos syndrome caused by mutant ZIP13 proteins

“…A mouse model of SCD‐EDS, the Slc39a13/Zip13‐ deficient ( Zip13 ‐KO) mouse, has features similar to those of human patients, that is, abnormal development of the skin, bone, teeth, and craniofacial structures. (Fukada et al , , ; Munemasa et al , ). Molecular analyses revealed that the mesenchymal‐originated cells from Zip13 ‐KO mice have impaired BMP/TGF‐β signaling, indicating that ZIP13 is critical for the development of hard and connective tissues (Fukada et al , ).…”

Requirement of Zinc Transporter SLC39A7/ZIP7 for Dermal Development to Fine-Tune Endoplasmic Reticulum Function by Regulating Protein Disulfide Isomerase

“…Zinc is a biologically essential metal ion (Hara et al, 2017;Nishi, 1996;Solomons et al, 1976), which significantly influences growth in mammals (Fukada et al, 2014). Zinc deficiency affects the development of connective tissues such as skin and bone (MacDonald, 2000;Prasad, 2013).…”

Morphometric analysis of cornea in the <i>Slc39a13</i>/<i>Zip13</i>-knockout mice

“…SLC39A13/ZIP13 is a member of the SLC39/ZIP zinc transporter family localizing mainly in the Golgi apparatus of osteoblasts, chondrocytes, odontoblasts and fibroblasts [ 5 ]. This protein involves in transporting zinc from the Golgi apparatus to the cytoplasm and controls the nuclear shift of SMAD proteins in TGF-β1 and bone morphogenetic protein (BMP) signaling pathways [ 2 , 3 , 7 , 16 ]. After the finding of mutation in SLC39A13/ZIP13 (ZIP13) of three gene types—i.e., B4GALT7 , B3GALT6 and ZIP13 , spondylodysplastic EDS- ZIP13 (spEDS- ZIP13 : OMIM 612350) was recognized as a new EDS type [ 5 , 8 , 13 ].…”