Mannan-binding lectin in diabetic kidney disease: the impact of mouse genetics in a type 1 diabetes model.
BACKGROUND. Mannan-binding lectin (MBL) is involved in the development of diabetic nephropathy. MBL is a part of the innate immune system where it can activate the complement system. Serum MBL level predicts later renal impairment in diabetes patients. Direct involvement of MBL in the development of diabetic kidney disease is observed in one animal strain. However, this involvement may differ among the animal strains. We thus examined the impact of the genetic background on the role of MBL in diabetic nephropathy.


METHODS
C57BL/6JBomTac and 129S6/SvEvTac mice were compared. In both strains, experimental type 1 diabetes was induced in wild-type (WT) and MBL-knockout (MBL-KO) mice by streptozotocin. Nondiabetic WT and MBL-KO mice were used as controls. We tested if MBL modified the diabetes-induced kidney changes by two-way ANOVA allowing for interaction.


RESULTS
MBL aggravated diabetes-induced kidney growth and glomerulus enlargement in C57BL/6JBomTac mice. MBL did not modify diabetes effects on glomerular basement membrane thickness or mesangial volume in any strain. Diabetes-induced changes in renal gene transcription of growth factors and matrix components were unaffected by MBL.


CONCLUSIONS
Strain-specific MBL effects were found on downstream diabetic kidney changes. This emphasizes the importance of genetic background in this model of diabetic complications.
Department of Endocrinology and Internal Medicine, Aarhus University Hospital and The Medical Research Laboratories, Institute of Clinical Medicine, Faculty of Health Sciences, Aarhus University, 8000 Aarhus C, Denmark. jakob.oestergaard@dadlnet.dk
Jakob Appel
JA
Østergaard
Mette
M
Bjerre
Satish Posettihalli
SP
RamachandraRao
Kumar
K
Sharma
Jens Randel
JR
Nyengaard
Troels Krarup
TK
Hansen
Steffen
S
Thiel
Allan
A
Flyvbjerg
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D007668:Kidney / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D014158:Transcription, Genetic
D001786:Blood Glucose; D037601:Mannose-Binding Lectin