Gimap6-KO Mouse

GIMAP6, the GTPase of the immune-associated protein 6, is a gene crucial for autophagy, immune competence, and inflammation [1,2]. It is part of the GIMAP GTPase family, which are prominently expressed in the adaptive immune system. GIMAP6 is involved in pathways such as redox regulation, and its expression can be induced by IFN-γ, playing a critical role in antibacterial immunity [1].

In Gimap6-/-mice, there are defects in autophagy, redox regulation, and polyunsaturated fatty acid-containing lipids. Mice with Gimap6 gene deletion in T and B cell lineages have a 50-70% reduction in peripheral CD4+ and CD8+ T cells, along with autophagic disruption as indicated by increased levels of MAP1LC3B (especially lipidated LC3-II form) and S405-phosphorylation of SQSTM1, and an increased mitochondrial/cytoplasmic volume ratio and autophagosome numbers [2]. Gimap6-/-mice also died prematurely from microangiopathic glomerulosclerosis, likely due to GIMAP6 deficiency in kidney endothelial cells [1]. In human patients with GIMAP6 mutations, they show infections, lymphoproliferation, autoimmunity, and multiorgan vasculitis, along with defects in autophagy and redox regulation [1].

In conclusion, GIMAP6 is essential for normal autophagic processes and the maintenance of a normal peripheral adaptive immune system. Studies on Gimap6-/-mouse models have revealed its role in various disease-related conditions such as microangiopathic glomerulosclerosis in mice and inborn errors of immunity in humans, highlighting its significance in understanding immune-related diseases [1,2].

References:

1. Yao, Yikun, Du Jiang, Ping, Chao, Brittany N, Simon, Anna Katharina, Lenardo, Michael J. 2022. GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans. In The Journal of experimental medicine, 219, . doi:10.1084/jem.20201405. https://pubmed.ncbi.nlm.nih.gov/35551368/

2. Pascall, John C, Webb, Louise M C, Eskelinen, Eeva-Liisa, Attaf-Bouabdallah, Noudjoud, Butcher, Geoffrey W. 2018. GIMAP6 is required for T cell maintenance and efficient autophagy in mice. In PloS one, 13, e0196504. doi:10.1371/journal.pone.0196504. https://pubmed.ncbi.nlm.nih.gov/29718959/