Welcome To Website IAS

Hot news

Independence Award

- First Rank - Second Rank - Third Rank

Labour Award

- First Rank - Second Rank -Third Rank

National Award

 - Study on food stuff for animal(2005)

 - Study on rice breeding for export and domestic consumption(2005)


- Hybrid Maize by Single Cross V2002 (2003)

- Tomato Grafting to Manage Ralstonia Disease(2005)

- Cassava variety KM140(2010)

Website links
Vietnamese calendar
Visitors summary
 Curently online :  5
 Total visitors :  5629142

De novo germline mutation in the dual specificity phosphatase 10 gene accelerates autoimmune diabetes
Friday, 2021/11/26 | 07:15:31

 Anne-Perrine Foray, Sophie Candon, Sara Hildebrand, Cindy Marquet, Fabrice Valette, Coralie Pecquet, Sebastien Lemoine, Francina Langa-Vives, Michael Dumas, Peipei Hu, Pere Santamaria, Sylvaine You, Stephen Lyon, Lindsay Scott, Chun Hui Bu, Tao Wang, Darui Xu, Eva Marie Y. Moresco, Claudio Scazzocchio, Jean-François Bach, Bruce Beutler, and Lucienne Chatenoud


PNAS November 23, 2021 118 (47) e2112032118


The vast majority of autoimmune diseases are polygenic, and causal loci uncovered by genetic-mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this missing heritability include rare meaningful variants, rare copy number variations or deletions, epistasis, epigenetics, disease heterogeneity, and rare or infrequent variants that segregate within individual families (even within monozygotic twins). Here we demonstrate that experimental models of spontaneous autoimmune diseases may be invaluable tools to map rare germline variants impacting disease susceptibility traits. We identified a variant of the dual-specificity phosphatase 10 encoding gene that accelerates disease in an autoimmune type 1 diabetes model, the nonobese diabetic mouse.


Insulin-dependent or type 1 diabetes (T1D) is a polygenic autoimmune disease. In humans, more than 60 loci carrying common variants that confer disease susceptibility have been identified by genome-wide association studies, with a low individual risk contribution for most variants excepting those of the major histocompatibility complex (MHC) region (40 to 50% of risk); hence the importance of missing heritability due in part to rare variants. Nonobese diabetic (NOD) mice recapitulate major features of the human disease including genetic aspects with a key role for the MHC haplotype and a series of Idd loci. Here we mapped in NOD mice rare variants arising from genetic drift and significantly impacting disease risk. To that aim we established by selective breeding two sublines of NOD mice from our inbred NOD/Nck colony exhibiting a significant difference in T1D incidence. Whole-genome sequencing of high (H)- and low (L)-incidence sublines (NOD/NckH and NOD/NckL) revealed a limited number of subline-specific variants. Treating age of diabetes onset as a quantitative trait in automated meiotic mapping (AMM), enhanced susceptibility in NOD/NckH mice was unambiguously attributed to a recessive missense mutation of Dusp10, which encodes a dual specificity phosphatase. The causative effect of the mutation was verified by targeting Dusp10 with CRISPR-Cas9 in NOD/NckL mice, a manipulation that significantly increased disease incidence. The Dusp10 mutation resulted in islet cell down-regulation of type I interferon signature genes, which may exert protective effects against autoimmune aggression. De novo mutations akin to rare human susceptibility variants can alter the T1D phenotype.


See: https://www.pnas.org/content/118/47/e2112032118


Fig. 1.

Diabetes incidence in sublines of the NOD/Nck strain. (A) Incidence of T1D at generation 3 in five distinct sublines (A to E) established from the NOD/Nck strain by brother–sister mating of mice within individual litters. For further studies we concentrated on sublines A and B, which we named NOD/NckL (for low incidence) and NOD/NckH (for high incidence). (B) Incidence of T1D in NOD/NckH and NOD/NckL male mice followed from generation 3 up to generation 34. ****P < 0.0001, ***P < 0.001, *P < 0.05. (C) Incidence of T1D in NOD/NckH and NOD/NckL male mice derived from embryos frozen at generation 7 and revitalized. Actuarial survival curves were compared using the log-rank (Mantel–Cox) statistical test.

Back      Print      View: 51

[ Other News ]___________________________________________________
  • Genome-wide analysis of autophagy-associated genes in foxtail millet (Setaria italica L.) and characterization of the function of SiATG8a in conferring tolerance to nitrogen starvation in rice.
  • Arabidopsis small nucleolar RNA monitors the efficient pre-rRNA processing during ribosome biogenesis
  • XA21-specific induction of stress-related genes following Xanthomonas infection of detached rice leaves.
  • Reducing the Use of Pesticides with Site-Specific Application: The Chemical Control of Rhizoctonia solani as a Case of Study for the Management of Soil-Borne Diseases
  • OsJRL, a rice jacalin-related mannose-binding lectin gene, enhances Escherichia coli viability under high-salinity stress and improves salinity tolerance of rice.
  • Production of lipopeptide biosurfactants by Bacillus atrophaeus 5-2a and their potential use in microbial enhanced oil recovery.
  • GhABF2, a bZIP transcription factor, confers drought and salinity tolerance in cotton (Gossypium hirsutum L.).
  • Resilience of cassava (Manihot esculenta Crantz) to salinity: implications for food security in low-lying regions.
  • Cellulose synthase complexes act in a concerted fashion to synthesize highly aggregated cellulose in secondary cell walls of plants
  • No adverse effects of transgenic maize on population dynamics of endophytic Bacillus subtilis strain B916-gfp
  • Identification and expression analysis of OsLPR family revealed the potential roles of OsLPR3 and 5 in maintaining phosphate homeostasis in rice
  • Functional analysis of molecular interactions in synthetic auxin response circuits
  • Titanium dioxide nanoparticles strongly impact soil microbial function by affecting archaeal nitrifiers.
  • Inducible Expression of the De-Novo Designed Antimicrobial Peptide SP1-1 in Tomato Confers Resistance to Xanthomonas campestris pv. vesicatoria.
  • Toward combined delignification and saccharification of wheat straw by a laccase-containing designer cellulosome
  • SNP-based discovery of salinity-tolerant QTLs in a bi-parental population of rice (Oryza sativa)
  • Pinpointing genes underlying the quantitative trait loci for root-knot nematode resistance in palaeopolyploid soybean by whole genome resequencing.
  • Transcriptome- Assisted Label-Free Quantitative Proteomics Analysis Reveals Novel Insights into Piper nigrum -Phytophthora capsici Phytopathosystem.
  • Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants
  • Rapid hyperosmotic-induced Ca2+ responses in Arabidopsis thaliana exhibit sensory potentiation and involvement of plastidial KEA transporters


Designed & Powered by WEBSO CO.,LTD