Construction and validation of Hrd1 conditional knockout mice

• 1、Hunan University Cross Research Institute of Life Medicine

Abstract：Hematopoietic stem cells are the most totipotent cell types in the hematopoietic system, and their normal function is one of the necessary conditions for the body to maintain lifelong blood production. The dysfunction of hematopoietic stem cells can lead to hematopoietic failure or malignant hematopathy. Protein homeostasis plays a key role in maintaining hematopoietic stem cell function. Previous studies have found that Sel1L-Hrd1 is the most conserved branch of the endoplasmic reticulum related degradation pathway, and the genes of the endoplasmic reticulum related degradation pathway are specifically highly expressed in hematopoietic stem cells. By selectively knocking out Sel1L, a key transmembrane protein in this pathway, excessive proliferation and activation of hematopoietic stem cells were observed, ultimately leading to loss of hematopoietic reconstitution. However, the phenotypes of hematopoietic changes induced by Sel1L knockout were significantly different in different laboratories. Therefore, this study conditionally knocked out Hrd1, another key component of Sel1L-Hrd1 in the endoplasmic reticulum related degradation pathway, and constructed and verified the relevant mouse model, providing an important research tool for further exploring the function of Sel1L-Hrd1 ERAD in the hematopoietic system.

Keywords： Molecular Medicine；Endoplasmic Reticulum-Associated Degradation Pathway； Hematopoietic Stem Cells ；Sel1L；Hrdl