Related Experiment Video
Updated: May 30, 2026
06:11
Monitoring Blood Glucose in Mouse Offspring After Intracytoplasmic Sperm Injection
Published on: May 17, 2024
Sox9-haploinsufficiency causes glucose intolerance in mice
Claire L Dubois1, Hung Ping Shih, Philip A Seymour
1Department of Pediatrics and Cellular & Molecular Medicine, University of California San Diego, La Jolla, California, United States of America.
Plos One
|August 11, 2011
Summary
Sox9 is crucial for pancreatic endocrine cell development and maintaining beta-cell mass. Reduced Sox9 dosage impairs glucose homeostasis, suggesting a role in human diabetes.
Area of Science:
- Developmental biology
- Endocrinology
- Genetics
Background:
- Sox9 is a transcription factor vital for pancreas development.
- In vitro studies suggested Sox9 regulates Tcf2, Hnf6, and Foxa2 in pancreatic progenitors.
- The in vivo role of Sox9 in regulating these factors and its impact on glucose homeostasis remained unclear.
Purpose of the Study:
- To determine if Sox9 regulates Tcf2, Hnf6, and Foxa2 in vivo.
- To investigate the effect of reduced Sox9 gene dosage on glucose homeostasis in adult mice.
- To elucidate the role of Sox9 in pancreatic beta-cell development and function.
Main Methods:
- Utilized two genetic models for temporal Sox9 inactivation in pancreatic progenitor cells.
- Analyzed gene expression of Tcf2, Hnf6, Foxa2, Pdx1, and Ngn3.
- Assessed beta-cell mass, proliferation, and glucose tolerance in Sox9-haploinsufficient mice.
Main Results:
- Sox9 is not required for Tcf2, Hnf6, or Foxa2 expression in vivo, contradicting in vitro findings.
- Sox9 is essential for maintaining Pdx1 expression, a key regulator of beta-cell development.
- Sox9-haploinsufficient mice exhibit reduced beta-cell mass and glucose intolerance in adulthood.
- Compensatory beta-cell proliferation partially restored mass postnatally, but insulin secretion remained normal.
Conclusions:
- Sox9 plays a critical role in pancreatic endocrine development by regulating Ngn3 and Pdx1 expression.
- Reduced Sox9 dosage leads to impaired glucose homeostasis due to decreased beta-cell mass.
- Mutations in Sox9 may contribute to the development of diabetes in humans.
Related Concept Videos
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
01:27Glucose Transporters
Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
02:32Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...