title: The physiological effects of deleting the mouse SLC30A8 gene encoding zinc transporter-8 are influenced by gender and genetic background.
abstract: OBJECTIVE
  The SLC30A8 gene encodes the islet-specific transporter ZnT-8, which is hypothesized to provide zinc for insulin-crystal formation. A polymorphic variant in SLC30A8 is associated with altered susceptibility to type 2 diabetes. Several groups have examined the effect of global Slc30a8 gene deletion but the results have been highly variable, perhaps due to the mixed 129SvEv/C57BL/6J genetic background of the mice studied. We therefore sought to remove the conflicting effect of 129SvEv-specific modifier genes.
  
  
  METHODS
  The impact of Slc30a8 deletion was examined in the context of the pure C57BL/6J genetic background.
  
  
  RESULTS
  Male C57BL/6J Slc30a8 knockout (KO) mice had normal fasting insulin levels and no change in glucose-stimulated insulin secretion (GSIS) from isolated islets in marked contrast to the ∼50% and ∼35% decrease, respectively, in both parameters observed in male mixed genetic background Slc30a8 KO mice. This observation suggests that 129SvEv-specific modifier genes modulate the impact of Slc30a8 deletion. In contrast, female C57BL/6J Slc30a8 KO mice had reduced (∼20%) fasting insulin levels, though this was not associated with a change in fasting blood glucose (FBG), or GSIS from isolated islets. This observation indicates that gender also modulates the impact of Slc30a8 deletion, though the physiological explanation as to why impaired insulin secretion is not accompanied by elevated FBG is unclear. Neither male nor female C57BL/6J Slc30a8 KO mice showed impaired glucose tolerance.
  
  
  CONCLUSIONS
  Our data suggest that, despite a marked reduction in islet zinc content, the absence of ZnT-8 does not have a substantial impact on mouse physiology.
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee, USA.
authors: Lynley D
authors: LD
authors: Pound
authors: Suparna A
authors: SA
authors: Sarkar
authors: Alessandro
authors: A
authors: Ustione
authors: Prasanna K
authors: PK
authors: Dadi
authors: Melanie K
authors: MK
authors: Shadoan
authors: Catherine E
authors: CE
authors: Lee
authors: Jay A
authors: JA
authors: Walters
authors: Masakazu
authors: M
authors: Shiota
authors: Owen P
authors: OP
authors: McGuinness
authors: David A
authors: DA
authors: Jacobson
authors: David W
authors: DW
authors: Piston
authors: John C
authors: JC
authors: Hutton
authors: David R
authors: DR
authors: Powell
authors: Richard M
authors: RM
authors: O'Brien
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D005215:Fasting / Q000097:blood*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000235:genetics; D007328:Insulin / Q000097:blood* / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012737:Sex Factors; D015032:Zinc / Q000378:metabolism; D000075703:Zinc Transporter 8
chemical_list: D001786:Blood Glucose; D027682:Cation Transport Proteins; D007328:Insulin; C516348:Slc30a8 protein, mouse; D000075703:Zinc Transporter 8; D015032:Zinc