Reduced body weight in male Tspan8-deficient mice

Abstract

Objective: The gene TSPAN8 was recently identified in a genome-wide association study as the most likely causal gene in a locus that was correlated with the risk of type 2 diabetes (T2D) in northern European individuals. To assess whether Tspan8 is the actual T2D-causal gene in this locus, we ablated its expression in mice and determined the consequences of this ablation on a multitude of metabolic traits. Results: We found that genetic ablation of Tspan8 in mice results in a reduction (À15.6%) in the body weight of males fed a normal chow diet and that this deficiency results in a resistance to body weight gain (À13.7%) upon feeding a high fat and high carbohydrate diet. The differences in body weight could only be detected in male mice and were the consequence of both a decrease in fat deposition, and a decrease in lean body mass (16.9 and 11%, respectively). In spite of the significant body weight difference, no changes in fasting insulin and glucose levels could be detected in Tspan8 knockout mice, nor could we identify changes in the clearance of glucose or sensitivity to insulin in oral glucose tolerance test and intraperitoneal insulin sensitivity test studies, respectively. In addition, male Tspan8 knockout mice showed significantly lower bone mineral density and phosphorus levels (6.2 and 16.6%, respectively). Expression of Tspan8 in mouse was highest in digestive tissues, but virtually absent from the pancreas. In contrast, expression of human TSPAN8 was substantial in digestive tissues, as well as pancreatic cells. Conclusions: Our results argue for a role for Tspan8 in body-weight regulation in males, but do not show differences in T2D-associated traits that were anticipated from previous human genome-wide association studies. Differences in Tspan8 expression levels in mouse and human tissues suggest that Tspan8 could fulfill different or additional physiological functions in these organisms.

Diabetes genes identified by genome-wide association studies are regulated in mice by nutritional factors in metabolically relevant tissues and by glucose concentrations in islets

“…Loss of this gene is associated with decreased body weight, although there were no detectable effects on glucose tolerance or insulin sensitivity [79]. In contrast to that study which did not detect expression of this gene in mouse pancreas [79], we found expression of this gene in isolated pancreatic islets and suggested regulation of its expression by glucose. Tspan8 expression was significantly decreased in brains of fed compared to fasted chow-fed mice, suggesting it may also have a role in the neural control of metabolism.…”

“…Although some studies have found associations between SNPs in this gene and insulin sensitivity or secretion [47,57], others have not [48-50,52]. Loss of this gene is associated with decreased body weight, although there were no detectable effects on glucose tolerance or insulin sensitivity [79]. In contrast to that study which did not detect expression of this gene in mouse pancreas [79], we found expression of this gene in isolated pancreatic islets and suggested regulation of its expression by glucose.…”

Proteomic markers of low and high fertility bovine spermatozoa separated by Percoll gradient

“…TSPAN8 has also been identified in the bovine sperm plasma membrane (Byrne et al, ), but no function has been attributed in sperm physiology. Male Tspan8 −/− mice are fertile and viable with no major abnormalities (Champy et al, ). As highlighted by these authors, most ablation of tetraspanins leads to viable mice without major developmental abnormalities, suggesting molecular redundancy or compensation.…”

Identification of cold responsive genes in Pacific white shrimp (Litopenaeus vannamei) by suppression subtractive hybridization

“…Still another role for TSPAN8 is seen during kidney disease in Humans; where TSPAN8 is believed serve a protective role (Pan et al). TSPAN8 may also provide protection during cold stress by forming membrane microdomains with other proteins to maintain membrane cryostability and fluidity, which is essential for resisting low temperature stress (Champy et al;Hirukawa et al;Cossins and Prosser, 1978).…”