Hmgn3-KO Mouse

Hmgn3, also known as high mobility group nucleosomal binding domain 3, is a member of the HMGN family. It binds to nucleosomes, modulates chromatin structure, and regulates transcription through interaction with transcription factors [1,4]. This gene is involved in multiple biological processes such as cell migration, differentiation, and decidualization, and is associated with various diseases including cholangiocarcinoma and early-onset preeclampsia [1,2]. Genetic models like gene knockout (KO) mice are valuable for studying Hmgn3's functions.

In Hmgn3-deficient mice, glucose-stimulated insulin secretion is impaired, leading to a diabetic phenotype. Hmgn3 affects the transcription of genes related to glucose-stimulated insulin secretion in pancreatic beta cells, for example, it regulates GLUT2 protein levels through interaction with transcription factor PDX1 [3]. Also, Hmgn3 -/- mice have reduced glucagon levels in their blood, though the mechanism is not directly related to pancreatic alpha-cell function [5]. In the context of cancer, knockdown of Hmgn3 in cholangiocarcinoma cells significantly impairs their colony formation, migration, and invasion abilities. Hmgn3 represses the transcription of epithelial regulator genes in a SNAI2-dependent manner [1]. In early-onset preeclampsia, WTAP-mediated m6A modification of Hmgn3 mRNA affects trophoblast invasion [2].

In summary, Hmgn3 plays essential roles in processes like insulin and glucagon regulation, cell migration in cancer, and trophoblast invasion. The study of Hmgn3 KO mouse models has provided insights into its functions in diabetes-related conditions and cancer metastasis, highlighting its potential as a therapeutic target in these disease areas [1,3,5].

References:

1. Sorin, Supannika, Kubota, Sho, Hamidi, Sofiane, Sawanyawisuth, Kanlayanee, Sashida, Goro. . HMGN3 represses transcription of epithelial regulators to promote migration of cholangiocarcinoma in a SNAI2-dependent manner. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36, e22345. doi:10.1096/fj.202200386R. https://pubmed.ncbi.nlm.nih.gov/35635715/

2. Bian, Yue, Li, Jiapo, Shen, Hongfei, Song, Guiyu, Qiao, Chong. . WTAP dysregulation-mediated HMGN3-m6A modification inhibited trophoblast invasion in early-onset preeclampsia. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36, e22617. doi:10.1096/fj.202200700RR. https://pubmed.ncbi.nlm.nih.gov/36412513/

3. Ueda, Tetsuya, Furusawa, Takashi, Kurahashi, Toshihiro, Tessarollo, Lino, Bustin, Michael. 2009. The nucleosome binding protein HMGN3 modulates the transcription profile of pancreatic beta cells and affects insulin secretion. In Molecular and cellular biology, 29, 5264-76. doi:10.1128/MCB.00526-09. https://pubmed.ncbi.nlm.nih.gov/19651901/

4. Barkess, Gráinne, Postnikov, Yuri, Campos, Chrisanne D, Bustin, Michael, West, Katherine L. . The chromatin-binding protein HMGN3 stimulates histone acetylation and transcription across the Glyt1 gene. In The Biochemical journal, 442, 495-505. doi:10.1042/BJ20111502. https://pubmed.ncbi.nlm.nih.gov/22150271/

5. Kurahashi, Toshihiro, Furusawa, Takashi, Ueda, Tetsuya, Bustin, Michael. . The nucleosome binding protein HMGN3 is expressed in pancreatic alpha-cells and affects plasma glucagon levels in mice. In Journal of cellular biochemistry, 109, 49-57. doi:10.1002/jcb.22377. https://pubmed.ncbi.nlm.nih.gov/19885867/