PMID- 31435002
OWN - NLM
STAT- MEDLINE
DCOM- 20210107
LR  - 20210110
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 21
IP  - 1
DP  - 2020 Jan
TI  - The type 1 diabetes candidate gene Dexi does not affect disease risk in the 
      nonobese diabetic mouse model.
PG  - 71-77
LID - 10.1038/s41435-019-0083-y [doi]
AB  - Genome-wide association studies have implicated more than 50 genomic regions in 
      type 1 diabetes (T1D). A T1D region at chromosome 16p13.13 includes the candidate 
      genes CLEC16A and DEXI. Conclusive evidence as to which gene is causal for the 
      disease association of this region is missing. We previously reported that 
      Clec16a deficiency modified immune reactivity and protected against autoimmunity 
      in the nonobese diabetic (NOD) mouse model for T1D. However, the 
      diabetes-associated SNPs at 16p13.13 were described to also impact on DEXI 
      expression and others have argued that DEXI is the causal gene in this disease 
      locus. To help resolve whether DEXI affects disease, we generated Dexi knockout 
      (KO) NOD mice. We found that Dexi deficiency had no effect on the frequency of 
      diabetes. To test for possible interactions between Dexi and Clec16a, we 
      intercrossed Dexi KO and Clec16a knockdown (KD) NOD mice. Dexi KO did not modify 
      the disease protection afforded by Clec16a KD. We conclude that Dexi plays no 
      role in autoimmune diabetes in the NOD model. Our data provide strongly 
      suggestive evidence that CLEC16A, not DEXI, is causal for the T1D association of 
      variants in the 16p13.13 region.
FAU - Nieves-Bonilla, Janice M
AU  - Nieves-Bonilla JM
AD  - Graduate Program in Biological and Biomedical Sciences, Division of Medical 
      Sciences, Harvard Medical School, Boston, MA, USA.
AD  - Section for Immunobiology, Joslin Diabetes Center, Harvard Medical School, 
      Boston, MA, USA.
FAU - Kiaf, Badr
AU  - Kiaf B
AD  - Section for Immunobiology, Joslin Diabetes Center, Harvard Medical School, 
      Boston, MA, USA.
FAU - Schuster, Cornelia
AU  - Schuster C
AD  - Section for Immunobiology, Joslin Diabetes Center, Harvard Medical School, 
      Boston, MA, USA.
FAU - Kissler, Stephan
AU  - Kissler S
AD  - Section for Immunobiology, Joslin Diabetes Center, Harvard Medical School, 
      Boston, MA, USA. stephan.kissler@joslin.harvard.edu.
LA  - eng
GR  - R56 DK109954/DK/NIDDK NIH HHS/United States
GR  - T32 DK007260/DK/NIDDK NIH HHS/United States
GR  - P30 DK036836/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190822
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (CLEC16A protein, mouse)
RN  - 0 (DEXI protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Membrane Proteins)
RN  - 0 (Monosaccharide Transport Proteins)
SB  - IM
CIN - Genes Immun. 2020 Feb;21(2):79-82. PMID: 31570815
MH  - Animals
MH  - Autoimmunity
MH  - DNA-Binding Proteins/*genetics/metabolism
MH  - Diabetes Mellitus, Type 1/*genetics/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Lectins, C-Type/*genetics
MH  - Male
MH  - Membrane Proteins/*genetics/metabolism
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Monosaccharide Transport Proteins/*genetics
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Risk Factors
PMC - PMC7035193
MID - NIHMS1536535
COIS- CONFLICT OF INTEREST The authors declare that they have no conflicts of interest.
EDAT- 2019/08/23 06:00
MHDA- 2021/01/08 06:00
PMCR- 2020/02/27
CRDT- 2019/08/23 06:00
PHST- 2019/03/05 00:00 [received]
PHST- 2019/08/02 00:00 [accepted]
PHST- 2019/07/25 00:00 [revised]
PHST- 2019/08/23 06:00 [pubmed]
PHST- 2021/01/08 06:00 [medline]
PHST- 2019/08/23 06:00 [entrez]
PHST- 2020/02/27 00:00 [pmc-release]
AID - 10.1038/s41435-019-0083-y [pii]
AID - 10.1038/s41435-019-0083-y [doi]
PST - ppublish
SO  - Genes Immun. 2020 Jan;21(1):71-77. doi: 10.1038/s41435-019-0083-y. Epub 2019 Aug 
      22.