Spin4-KO Mouse

SPIN4, also known as Spindlin-4, is a Tudor domain-containing protein. It is a principal endogenous substrate of the E3 ubiquitin ligase DCAF16 [1]. SPIN4 preferentially binds trimethylated histone H3K4, and is involved in epigenetic regulation. It promotes canonical WNT signaling and inhibits cell proliferation, thus negatively regulating mammalian body growth [2].

A loss-of-function frameshift variant in SPIN4 was identified in a male individual with generalized overgrowth of prenatal onset, indicating an X-linked overgrowth syndrome [2]. Ablation of Spin4 in mice recapitulated the human phenotype with generalized overgrowth, including increased longitudinal bone growth. Growth plate analysis showed increased cell proliferation in the proliferative zone and more progenitor chondrocytes in the resting zone, along with decreased canonical Wnt signaling in growth plate chondrocytes [2].

In conclusion, SPIN4 is an epigenetic reader that plays a crucial role in negatively regulating mammalian body growth. The discovery from Spin4 knockout mouse models provides strong evidence for its role in an X-linked overgrowth syndrome, expanding our understanding of the epigenetic regulation of human growth [2].

References:

1. Zhang, Xiaoyu, Thielert, Marvin, Li, Haoxin, Cravatt, Benjamin F. 2021. SPIN4 Is a Principal Endogenous Substrate of the E3 Ubiquitin Ligase DCAF16. In Biochemistry, 60, 637-642. doi:10.1021/acs.biochem.1c00067. https://pubmed.ncbi.nlm.nih.gov/33636084/

2. Lui, Julian C, Wagner, Jacob, Zhou, Elaine, Jee, Youn Hee, Baron, Jeffrey. 2023. Loss-of-function variant in SPIN4 causes an X-linked overgrowth syndrome. In JCI insight, 8, . doi:10.1172/jci.insight.167074. https://pubmed.ncbi.nlm.nih.gov/36927955/