In order to provide molecular biological basis for breeding of excellent seedless varieties of Siraitia grosvenorii, the genetic background of 28 female triploid and male diploid individuals of S. grosvenorii was anal...In order to provide molecular biological basis for breeding of excellent seedless varieties of Siraitia grosvenorii, the genetic background of 28 female triploid and male diploid individuals of S. grosvenorii was analyzed by using RAPD molecular markers. The results showed that female triploid and male diploid individuals of S. grosvenorli had abundant genetic background, with great genetic similarity cecfficients and close genetic distance. Overall, the genetic background of female triploid and male diploid individuals of S. grosvenorii exhibited relatively low complexity. Therefore, it is necessary to take corresponding measures for germplasm innovation to enrich the genetic background of seedless parents of S. grosvenorii.展开更多
HBV infection data of so first degree relatives from hepatitis B vaccine nonresponderand hyporesponder families stere compared 'vith those of 79 first degree relatives from high responder families. For further obs...HBV infection data of so first degree relatives from hepatitis B vaccine nonresponderand hyporesponder families stere compared 'vith those of 79 first degree relatives from high responder families. For further observation of their antibody response. those without the vaccination lwfore, and negative for HBsAg, anti-HBs and anti-HBc, or 'vith isolated ic'v anti-HBs (S/N M 10 )were given three 10 ig doses of hepatitis B vaccine at 0, 1 .6 months. The results Showed that. in thefirst degree relatives of nonresponders and hyporesponders, anti-HBs seroconversion rate and GMTwere lower (P > 0. 05), and the distribution or detected anti-HBs levels was significantly differentfrom that of the rirst degree relatives or high respondrs. In addition, before the vaccination. theHBV infection rate or the former was remarkably higher (33. 75% VS 15. 19% ), and the antibodyGMT of those positive ror anti-HBs was significantly ic'ver. This finding suggested that genetic background may play an important role in the n on -a nd-typo res ponsi yeness to hepat it is B vacc me.展开更多
The intestinal microbiome has emerged as an important component involved in various diseases.Therefore,the interest in understanding the factors shaping its composition is growing.The gut microbiome,often defined as a...The intestinal microbiome has emerged as an important component involved in various diseases.Therefore,the interest in understanding the factors shaping its composition is growing.The gut microbiome,often defined as a complex trait,contains diverse components and its properties are determined by a combination of external and internal effects.Although much effort has been invested so far,it is still difficult to evaluate the extent to which human genetics shape the composition of the gut microbiota.However,in mouse studies,where the environmental factors are better controlled,the effect of the genetic background was significant.The purpose of this paper is to provide a current assessment of the role of human host genetics in shaping the gut microbiome composition.Despite the inconsistency of the reported results,it can be estimated that the genetic factor affects a portion of the microbiome.However,this effect is currently lower than the initial estimates,and it is difficult to separate the genetic influence from the environmental effect.Additionally,despite the differences between the microbial composition of humans and mice,results from mouse models can strengthen our knowledge of host genetics underlying the human gut microbial variation.展开更多
The generation fertility of 51 F1, 19 F2 and 6 BC1 between 3 thermo-sensitive genic male sterile lines (TGMS-lines) Pei'ai 64S, 6311S and 360S, and the three lines of hybrid rice including 7 indica cytoplasmic male...The generation fertility of 51 F1, 19 F2 and 6 BC1 between 3 thermo-sensitive genic male sterile lines (TGMS-lines) Pei'ai 64S, 6311S and 360S, and the three lines of hybrid rice including 7 indica cytoplasmic male sterile lines (CMS-lines) and their corresponding maintainer lines (B-lines) and 3 indica restorer lines (R-lines) were investigated to study the expression of TGMS-genes in the backgrounds of the three lines of hybrid rice. Pei'ai 64S has stronger fertility restoring (Rf) genes for CMS-lines and its TGMS trait is governed by 2 pairs of independent recessive genes; The TGMS trait of 6311S is governed by a single recessive gene with weaker Rf-gene in 6311S and the TGMS trait of 360S is governed by a single recessive gene with no Rf-gene in 360S. The investigation on the fertility of F1 plants between 5 CMS-lines and 4 TGMS generations selected from F2 plants of 4 CMS-lines x 6311S confirmed that the expression of TGMS-gene was controlled by Rf-gene in the genetic background of cytoplasm of CMS-lines, but not affected by Rf-gene in the genetic background of normal fertile cytoplasm. The potential breeding strategies of TGMS-lines with cytoplasm of CMS-lines and CMS-lines with the nucleus of TGMS-genes were discussed.展开更多
BACKGROUND Solitary rectal ulcer syndrome(SRUS)is a rare rectal disease with unknown etiology.Data on the genetic background in SRUS is lacking.CASE SUMMARY Here,we report the first case of SRUS in a mother-son relati...BACKGROUND Solitary rectal ulcer syndrome(SRUS)is a rare rectal disease with unknown etiology.Data on the genetic background in SRUS is lacking.CASE SUMMARY Here,we report the first case of SRUS in a mother-son relationship.Gene sequencing was conducted on the whole family,which revealed an inherited CHEK2 p.H371Y mutation.The experiment preliminarily revealed that the CHEK2 mutation did not affect the expression of CHEK2 protein,but affected the function of CHEK2,resulting in the expression level changes of downstream genes such as CDC25A.CONCLUSION SRUS is a genetic susceptibility disease where CHEK2 p.H371Y mutation may play a crucial role in the development and prognosis of SRUS.展开更多
Grain traits are major constraints in rice production, which are key factors in determining grain yield and market values. This study used two recombinant inbred line(RIL) populations, RIL-JJ(japonica/japonica) an...Grain traits are major constraints in rice production, which are key factors in determining grain yield and market values. This study used two recombinant inbred line(RIL) populations, RIL-JJ(japonica/japonica) and RIL-IJ(indica/japonica) derived from the two crosses Shennong 265/Lijiangxintuanheigu(SN265/LTH) and Shennong 265/Luhui 99(SN265/LH99). Sixty-eight quantitative trait loci(QTLs) associated with 10 grain traits were consistently detected on the 12 chromosomes across different populations and two environments. Although 61.75% of the QTLs clustered together across two populations, only 16.17% could be detected across two populations. Eight major QTLs were detected on the 9, 10 and 12 chromosomes in RIL-JJ under two environments, a novel QTL clustered on the 10 chromosome, q GT10, q BT10 and q TGW10, have a higher percentage of explained phenotypic variation(PVE) and additive effect; 15 major QTLs were detected on the 5, 8, 9, and 11 chromosomes in RIL-IJ under two environments, a novel clustered QTL, q GT8 and q TGW8, on the 8 chromosome have a higher additive effect. Finally, the analysis of major QTL-BSA mapping narrowed the q TGW10 to a 1.47-Mb region flanked by simple sequence repeat markers RM467 and RM6368 on chromosome 10. A comparison of QTLs for grain traits in two different genetic backgrounds recombinant inbred line populations confirmed that genetic background had a significant impact on grain traits. The identified QTLs were stable across different populations and various environments, and 29.42% of QTLs controlling grain traits were reliably detected in different environments. Fewer QTLs were detected for brown rice traits than for paddy rice traits, 7 and 17 QTLs for brown rice out of 25 and 43 QTLs under RIL-JJ and RILIJ populations, respectively. The identification of genes constituting the QTLs will help to further our understanding of the molecular mechanisms underlying grain shape.展开更多
There are few studies on the membrane protein Ankfyl. We have found Ankfyl is specifically expressed in neural stem/precursor cells during early development in mice (murine). To further explore Ankfyl function in ne...There are few studies on the membrane protein Ankfyl. We have found Ankfyl is specifically expressed in neural stem/precursor cells during early development in mice (murine). To further explore Ankfyl function in neural development, we developed a gene knockout mouse with a mixed Balb/C and C57/BL6 genetic background. Using immunofluorescence and in situ hybridization, neural defects were absent in mixed genetic Ankfyl null mice during development and in adults up to 2 months old. However, Ankfyl gene knockout mice with a pure genetic background were found to be lethal in the C57/BL6 inbred mice embryos, even after seven generations of backcrossing. Polymerase chain reaction confirmed homozygotes were unattainable as early as embryonic day 11.5. We conclude that Ankfyl protein is dispensable in neural stem/precursor ceils, but could be critical for early embryonic murine development, depending on the genetic background.展开更多
Peiai64S, an indica male sterile rice with a male fertility alteration under different environments, is selected from the offspring of indica rice crossed with Nongken58S. Nongken58S, a japonica pho-toperiod sensitive...Peiai64S, an indica male sterile rice with a male fertility alteration under different environments, is selected from the offspring of indica rice crossed with Nongken58S. Nongken58S, a japonica pho-toperiod sensitive genie male sterile rice (PGMS), deriving from a natural mutant plant individual of normal japonica rice variety, Nongken58, is used as a male sterile gene donor of Peiai64S. But Peiai64S is not a typical PGMS rice, the male fertility is sensitive to temperature just as thermo-sensitive genie male sterile rice (TGMS). We have selected typical PGMS plants in F2 population of Peiai64S× Nongken58, whose ratio of fertile plants to sterile plants is nearly 3:1. The sterility inheritance conformed to one pair of gene segregation model. The result indicates the main male sterile gene in Peiai64S is not other than the PGMS gene, and comes from Nongken58S. The genetic background affects effective expression of the PGMS gene. This suggests that we ought to focus on optimizing the genetic background of the PGMS gene in PGMS rice breeding, and select an ideal genetic background as a transgenic background in molecular breeding.展开更多
The leading-edge CRISPR/CRISPR-associated technology is revolutionizing biotechnologies through genome editing.To track on/off-target events with emerging new editing techniques,improved bioinformatic tools are indisp...The leading-edge CRISPR/CRISPR-associated technology is revolutionizing biotechnologies through genome editing.To track on/off-target events with emerging new editing techniques,improved bioinformatic tools are indispensable.Existing tools suffer from limitations in speed and scalability,especially with whole-genome sequencing(WGS)data analysis.To address these limitations,we have developed a comprehensive tool called CRISPR-detector,a web-based and locally deployable pipeline for genome editing sequence analysis.The core analysis module of CRISPR-detector is based on the Sentieon TNscope pipeline,with additional novel annotation and visualization modules designed to fit CRISPR applications.Co-analysis of the treated and control samples is performed to remove existing background variants prior to genome editing.CRISPR-detector offers optimized scalability,enabling WGS data analysis beyond Browser Extensible Data file-defined regions,with improved accuracy due to haplotype-based variant calling to handle sequencing errors.In addition,the tool also provides integrated structural variation calling and includes functional and clinical annotations of editing-induced mutations appreciated by users.These advantages facilitate rapid and efficient detection of mutations induced by genome editing events,especially for datasets generated from WGS.The web-based version of CRISPR-detector is available at https://db.cngb.org/crispr-detector,and the locally deployable version is available at https://github.com/hlcas/CRISPR-detector.展开更多
Beef and mutton production has been aided by breeding to integrate allelic diversity for myostatin(MSTN),but a lack of diversity in the MSTN germplasm has limited similar advances in pig farming.Moreover,insurmountabl...Beef and mutton production has been aided by breeding to integrate allelic diversity for myostatin(MSTN),but a lack of diversity in the MSTN germplasm has limited similar advances in pig farming.Moreover,insurmountable challenges with congenital lameness and a dearth of data about the impacts of feed conversion,reproduction,and meat quality in MSTN-edited pigs have also currently blocked progress.Here,in a largest-to-date evaluation of multiple MSTN-edited pig populations,we demonstrated a practical alternative edit-site-based solution that overcomes the major production obstacle of hindlimb weakness.We also provide long-term and multidomain datasets for multiple breeds that illustrate how MSTN-editing can sustainably increase the yields of breed-specific lean meat and the levels of desirable lipids without deleteriously affecting feed-conversion rates or litter size.Apart from establishing a new benchmark for the data scale and quality of genome-edited animal production,our study specifically illustrates how gene-editing site selection profoundly impacts the phenotypic outcomes in diverse genetic back-grounds.展开更多
The recognition of p-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immuni...The recognition of p-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BIJ6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-l-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th I responses. In contrast, the resistance of dectin- 1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Thl/Treg immune responses that provide immunological memory. Disparate canonical/ noncanonical NF-KB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling.展开更多
基金Supported by National Science&Technology Supporting Program of China(2011BAI01B03)National Natural Science Foundation of China(81373914)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2013GXNSFDA019021,2013GXNSFBA019170,2015GXNSFBA139149,2015GX NSFBA139134)
文摘In order to provide molecular biological basis for breeding of excellent seedless varieties of Siraitia grosvenorii, the genetic background of 28 female triploid and male diploid individuals of S. grosvenorii was analyzed by using RAPD molecular markers. The results showed that female triploid and male diploid individuals of S. grosvenorli had abundant genetic background, with great genetic similarity cecfficients and close genetic distance. Overall, the genetic background of female triploid and male diploid individuals of S. grosvenorii exhibited relatively low complexity. Therefore, it is necessary to take corresponding measures for germplasm innovation to enrich the genetic background of seedless parents of S. grosvenorii.
文摘HBV infection data of so first degree relatives from hepatitis B vaccine nonresponderand hyporesponder families stere compared 'vith those of 79 first degree relatives from high responder families. For further observation of their antibody response. those without the vaccination lwfore, and negative for HBsAg, anti-HBs and anti-HBc, or 'vith isolated ic'v anti-HBs (S/N M 10 )were given three 10 ig doses of hepatitis B vaccine at 0, 1 .6 months. The results Showed that. in thefirst degree relatives of nonresponders and hyporesponders, anti-HBs seroconversion rate and GMTwere lower (P > 0. 05), and the distribution or detected anti-HBs levels was significantly differentfrom that of the rirst degree relatives or high respondrs. In addition, before the vaccination. theHBV infection rate or the former was remarkably higher (33. 75% VS 15. 19% ), and the antibodyGMT of those positive ror anti-HBs was significantly ic'ver. This finding suggested that genetic background may play an important role in the n on -a nd-typo res ponsi yeness to hepat it is B vacc me.
基金Binational Science Foundation(BSF)grant number 2015077German Israeli Science Foundation(GIF)grant I-63-410.20-2017,Israeli Science Foundation(ISF)grant 1085/18,and Core Fund Form Tel-Aviv University.
文摘The intestinal microbiome has emerged as an important component involved in various diseases.Therefore,the interest in understanding the factors shaping its composition is growing.The gut microbiome,often defined as a complex trait,contains diverse components and its properties are determined by a combination of external and internal effects.Although much effort has been invested so far,it is still difficult to evaluate the extent to which human genetics shape the composition of the gut microbiota.However,in mouse studies,where the environmental factors are better controlled,the effect of the genetic background was significant.The purpose of this paper is to provide a current assessment of the role of human host genetics in shaping the gut microbiome composition.Despite the inconsistency of the reported results,it can be estimated that the genetic factor affects a portion of the microbiome.However,this effect is currently lower than the initial estimates,and it is difficult to separate the genetic influence from the environmental effect.Additionally,despite the differences between the microbial composition of humans and mice,results from mouse models can strengthen our knowledge of host genetics underlying the human gut microbial variation.
文摘The generation fertility of 51 F1, 19 F2 and 6 BC1 between 3 thermo-sensitive genic male sterile lines (TGMS-lines) Pei'ai 64S, 6311S and 360S, and the three lines of hybrid rice including 7 indica cytoplasmic male sterile lines (CMS-lines) and their corresponding maintainer lines (B-lines) and 3 indica restorer lines (R-lines) were investigated to study the expression of TGMS-genes in the backgrounds of the three lines of hybrid rice. Pei'ai 64S has stronger fertility restoring (Rf) genes for CMS-lines and its TGMS trait is governed by 2 pairs of independent recessive genes; The TGMS trait of 6311S is governed by a single recessive gene with weaker Rf-gene in 6311S and the TGMS trait of 360S is governed by a single recessive gene with no Rf-gene in 360S. The investigation on the fertility of F1 plants between 5 CMS-lines and 4 TGMS generations selected from F2 plants of 4 CMS-lines x 6311S confirmed that the expression of TGMS-gene was controlled by Rf-gene in the genetic background of cytoplasm of CMS-lines, but not affected by Rf-gene in the genetic background of normal fertile cytoplasm. The potential breeding strategies of TGMS-lines with cytoplasm of CMS-lines and CMS-lines with the nucleus of TGMS-genes were discussed.
基金This work was supported by the Guangdong Basic and Applied Basic Research Fund,No.2022A1515111193the Guangzhou Science and technology plan project,No.2023A04J0581.
文摘BACKGROUND Solitary rectal ulcer syndrome(SRUS)is a rare rectal disease with unknown etiology.Data on the genetic background in SRUS is lacking.CASE SUMMARY Here,we report the first case of SRUS in a mother-son relationship.Gene sequencing was conducted on the whole family,which revealed an inherited CHEK2 p.H371Y mutation.The experiment preliminarily revealed that the CHEK2 mutation did not affect the expression of CHEK2 protein,but affected the function of CHEK2,resulting in the expression level changes of downstream genes such as CDC25A.CONCLUSION SRUS is a genetic susceptibility disease where CHEK2 p.H371Y mutation may play a crucial role in the development and prognosis of SRUS.
基金supported by the National Natural Science Foundation of China(31371586)the Program for Liaoning Excellent Talents in University,China(LJQ2013075)
文摘Grain traits are major constraints in rice production, which are key factors in determining grain yield and market values. This study used two recombinant inbred line(RIL) populations, RIL-JJ(japonica/japonica) and RIL-IJ(indica/japonica) derived from the two crosses Shennong 265/Lijiangxintuanheigu(SN265/LTH) and Shennong 265/Luhui 99(SN265/LH99). Sixty-eight quantitative trait loci(QTLs) associated with 10 grain traits were consistently detected on the 12 chromosomes across different populations and two environments. Although 61.75% of the QTLs clustered together across two populations, only 16.17% could be detected across two populations. Eight major QTLs were detected on the 9, 10 and 12 chromosomes in RIL-JJ under two environments, a novel QTL clustered on the 10 chromosome, q GT10, q BT10 and q TGW10, have a higher percentage of explained phenotypic variation(PVE) and additive effect; 15 major QTLs were detected on the 5, 8, 9, and 11 chromosomes in RIL-IJ under two environments, a novel clustered QTL, q GT8 and q TGW8, on the 8 chromosome have a higher additive effect. Finally, the analysis of major QTL-BSA mapping narrowed the q TGW10 to a 1.47-Mb region flanked by simple sequence repeat markers RM467 and RM6368 on chromosome 10. A comparison of QTLs for grain traits in two different genetic backgrounds recombinant inbred line populations confirmed that genetic background had a significant impact on grain traits. The identified QTLs were stable across different populations and various environments, and 29.42% of QTLs controlling grain traits were reliably detected in different environments. Fewer QTLs were detected for brown rice traits than for paddy rice traits, 7 and 17 QTLs for brown rice out of 25 and 43 QTLs under RIL-JJ and RILIJ populations, respectively. The identification of genes constituting the QTLs will help to further our understanding of the molecular mechanisms underlying grain shape.
基金Dr.Hui Fu was supported by the National Natural Science Foundation of China,No.81371338by Open Research Fund Program of Hubei-MOST KLOS & KLOBMEDr.Zu-neng Lu was supported by grants from Health and Family Planning Commission of Hubei Province scientific research project,No.WJ2015MA007
文摘There are few studies on the membrane protein Ankfyl. We have found Ankfyl is specifically expressed in neural stem/precursor cells during early development in mice (murine). To further explore Ankfyl function in neural development, we developed a gene knockout mouse with a mixed Balb/C and C57/BL6 genetic background. Using immunofluorescence and in situ hybridization, neural defects were absent in mixed genetic Ankfyl null mice during development and in adults up to 2 months old. However, Ankfyl gene knockout mice with a pure genetic background were found to be lethal in the C57/BL6 inbred mice embryos, even after seven generations of backcrossing. Polymerase chain reaction confirmed homozygotes were unattainable as early as embryonic day 11.5. We conclude that Ankfyl protein is dispensable in neural stem/precursor ceils, but could be critical for early embryonic murine development, depending on the genetic background.
基金supported by the 9th“Five-Year-Plan”key technology projects in the Bio tech field of“863”program.
文摘Peiai64S, an indica male sterile rice with a male fertility alteration under different environments, is selected from the offspring of indica rice crossed with Nongken58S. Nongken58S, a japonica pho-toperiod sensitive genie male sterile rice (PGMS), deriving from a natural mutant plant individual of normal japonica rice variety, Nongken58, is used as a male sterile gene donor of Peiai64S. But Peiai64S is not a typical PGMS rice, the male fertility is sensitive to temperature just as thermo-sensitive genie male sterile rice (TGMS). We have selected typical PGMS plants in F2 population of Peiai64S× Nongken58, whose ratio of fertile plants to sterile plants is nearly 3:1. The sterility inheritance conformed to one pair of gene segregation model. The result indicates the main male sterile gene in Peiai64S is not other than the PGMS gene, and comes from Nongken58S. The genetic background affects effective expression of the PGMS gene. This suggests that we ought to focus on optimizing the genetic background of the PGMS gene in PGMS rice breeding, and select an ideal genetic background as a transgenic background in molecular breeding.
基金supported by the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ13-YQ-095 and ZZXT201708)the Start-up Research Fund from BNU-HKBU United International College(UICR0700053-23).
文摘The leading-edge CRISPR/CRISPR-associated technology is revolutionizing biotechnologies through genome editing.To track on/off-target events with emerging new editing techniques,improved bioinformatic tools are indispensable.Existing tools suffer from limitations in speed and scalability,especially with whole-genome sequencing(WGS)data analysis.To address these limitations,we have developed a comprehensive tool called CRISPR-detector,a web-based and locally deployable pipeline for genome editing sequence analysis.The core analysis module of CRISPR-detector is based on the Sentieon TNscope pipeline,with additional novel annotation and visualization modules designed to fit CRISPR applications.Co-analysis of the treated and control samples is performed to remove existing background variants prior to genome editing.CRISPR-detector offers optimized scalability,enabling WGS data analysis beyond Browser Extensible Data file-defined regions,with improved accuracy due to haplotype-based variant calling to handle sequencing errors.In addition,the tool also provides integrated structural variation calling and includes functional and clinical annotations of editing-induced mutations appreciated by users.These advantages facilitate rapid and efficient detection of mutations induced by genome editing events,especially for datasets generated from WGS.The web-based version of CRISPR-detector is available at https://db.cngb.org/crispr-detector,and the locally deployable version is available at https://github.com/hlcas/CRISPR-detector.
基金the National Major Transgenic Breeding Project(2008ZX08006-003,2011ZX08006-003,2013ZX08006-003,2014ZX08006-003,and 2016ZX08006-001)the Na-tional Key Basic Research Development Plan(2015CB943100)+1 种基金the Key Projects of the National Natural Science Foundation of China(30830080 and 31330074)China Postdoctoral Foundation Project(2018M631648)。
文摘Beef and mutton production has been aided by breeding to integrate allelic diversity for myostatin(MSTN),but a lack of diversity in the MSTN germplasm has limited similar advances in pig farming.Moreover,insurmountable challenges with congenital lameness and a dearth of data about the impacts of feed conversion,reproduction,and meat quality in MSTN-edited pigs have also currently blocked progress.Here,in a largest-to-date evaluation of multiple MSTN-edited pig populations,we demonstrated a practical alternative edit-site-based solution that overcomes the major production obstacle of hindlimb weakness.We also provide long-term and multidomain datasets for multiple breeds that illustrate how MSTN-editing can sustainably increase the yields of breed-specific lean meat and the levels of desirable lipids without deleteriously affecting feed-conversion rates or litter size.Apart from establishing a new benchmark for the data scale and quality of genome-edited animal production,our study specifically illustrates how gene-editing site selection profoundly impacts the phenotypic outcomes in diverse genetic back-grounds.
文摘The recognition of p-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BIJ6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-l-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th I responses. In contrast, the resistance of dectin- 1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Thl/Treg immune responses that provide immunological memory. Disparate canonical/ noncanonical NF-KB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling.