The targeted Arhgef11 gene encodes PDZ-RhoGEF, a Rho GTPase that is involved in cell signaling, cell migration, chemotaxis, neurite outgrowth, as well as metabolic homeostasis. Mutations in this gene have been associated with obesity and type 2 diabetes.
These knock-out mice carry a mutation in which exon 2 has been deleted via Cre-mediated recombination. No gene product (protein) is detected by Western blot analysis of MEFs isolated from homozygotes.
Mice that are homozygous for the targeted mutation are viable and fertile, but are smaller in size than wildtype controls. Homozygotes exhibit lower body fat index with reduced major fat depots (epididymal, knee, inguinal, and retroperitoneal white adipose tissue) when compared to controls, and a slight reduction in brown adipose tissue mass.
Fewer mature adipocytes are found in white adipose. MEFs from mutant mice exhibit reduced cell proliferation.
Homozygotes on a high fat diet do not develop obesity, glucose intolerance or insulin resistance.
Total oxygen consumption is increased in homozygotes, and there is a trend to increased total activity.
During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.
