当前位置： SCI文献检索 > AMERICAN JOURNAL OF HUMAN GENETICS期刊下所有文献 > Apigenin as a Candidate Prenatal Treatment for Trisomy 21: Effects in Human Amniocytes and the Ts1Cje Mouse Model.

Apigenin as a Candidate Prenatal Treatment for Trisomy 21: Effects in Human Amniocytes and the Ts1Cje Mouse Model.

Abstract：

:Human fetuses with trisomy 21 (T21) have atypical brain development that is apparent sonographically in the second trimester. We hypothesize that by analyzing and integrating dysregulated gene expression and pathways common to humans with Down syndrome (DS) and mouse models we can discover novel targets for prenatal therapy. Here, we tested the safety and efficacy of apigenin, identified with this approach, in both human amniocytes from fetuses with T21 and in the Ts1Cje mouse model. In vitro, T21 cells cultured with apigenin had significantly reduced oxidative stress and improved antioxidant defense response. In vivo, apigenin treatment mixed with chow was administered prenatally to the dams and fed to the pups over their lifetimes. There was no significant increase in birth defects or pup deaths resulting from prenatal apigenin treatment. Apigenin significantly improved several developmental milestones and spatial olfactory memory in Ts1Cje neonates. In addition, we noted sex-specific effects on exploratory behavior and long-term hippocampal memory in adult mice, and males showed significantly more improvement than females. We demonstrated that the therapeutic effects of apigenin are pleiotropic, resulting in decreased oxidative stress, activation of pro-proliferative and pro-neurogenic genes (KI67, Nestin, Sox2, and PAX6), reduction of the pro-inflammatory cytokines INFG, IL1A, and IL12P70 through the inhibition of NFκB signaling, increase of the anti-inflammatory cytokines IL10 and IL12P40, and increased expression of the angiogenic and neurotrophic factors VEGFA and IL7. These studies provide proof of principle that apigenin has multiple therapeutic targets in preclinical models of DS.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Guedj F,Siegel AE,Pennings JLA,Alsebaa F,Massingham LJ,Tantravahi U,Bianchi DW

doi

10.1016/j.ajhg.2020.10.001

subject

Has Abstract

pub_date

2020-11-05 00:00:00

pages

911-931

issue

5

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(20)30359-1

journal_volume

107

pub_type

杂志文章

相关文献

AMERICAN JOURNAL OF HUMAN GENETICS文献大全
  • Molecular and phenotypic analysis of patients with deletions within the deletion-rich region of the Duchenne muscular dystrophy (DMD) gene.

    abstract：:Eighty unrelated individuals with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) were found to have deletions in the major deletion-rich region of the DMD locus. This region includes the last five exons detected by cDNA5b-7, all exons detected by cDNA8, and the first two exons detected by cDNA9. ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Gillard EF,Chamberlain JS,Murphy EG,Duff CL,Smith B,Burghes AH,Thompson MW,Sutherland J,Oss I,Bodrug SE

    更新日期：1989-10-01 00:00:00

  • Testing for association between disease and linked marker loci: a log-linear-model analysis.

    abstract：:One approach frequently used for identifying genetic factors involved in the process of a complex disease is the comparison of patients and controls for a number of genetic markers near a candidate gene. The analysis of such association studies raises some specific problems because of the fact that genotypic and not g...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Tiret L,Amouyel P,Rakotovao R,Cambien F,Ducimetière P

    更新日期：1991-05-01 00:00:00

  • ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor.

    abstract：:Paget disease of bone (PDB) is a skeletal disorder characterized by focal abnormalities of bone remodeling, which result in enlarged and deformed bones in one or more regions of the skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2015.12.016

    authors： Divisato G,Formicola D,Esposito T,Merlotti D,Pazzaglia L,Del Fattore A,Siris E,Orcel P,Brown JP,Nuti R,Strazzullo P,Benassi MS,Cancela ML,Michou L,Rendina D,Gennari L,Gianfrancesco F

    更新日期：2016-02-04 00:00:00

  • Teaching human genetics in biochemistry by computer literature searching.

    abstract：:We describe a new user-intense-learning experience that incorporates the teaching of clinical and research applications of human genetics in biochemistry while training first-year medical students to develop skills in computer access to the literature. Human genetics was incorporated into the biochemistry curriculum b...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Proud VK,Schmidt FJ,Johnson ED,Mitchell JA

    更新日期：1989-04-01 00:00:00

  • Autism or atypical autism in maternally but not paternally derived proximal 15q duplication.

    abstract：:Duplications of proximal 15q have been found in individuals with autistic disorder (AD) and varying degrees of mental retardation. Often these abnormalities take the form of a supernumerary inverted duplicated chromosome 15, more properly described as an isodicentric chromosome 15, or idic(15). However, intrachromosom...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Cook EH Jr,Lindgren V,Leventhal BL,Courchesne R,Lincoln A,Shulman C,Lord C,Courchesne E

    更新日期：1997-04-01 00:00:00

  • Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1.

    abstract：:Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2011.10.002

    authors： Bown MJ,Jones GT,Harrison SC,Wright BJ,Bumpstead S,Baas AF,Gretarsdottir S,Badger SA,Bradley DT,Burnand K,Child AH,Clough RE,Cockerill G,Hafez H,Scott DJ,Futers S,Johnson A,Sohrabi S,Smith A,Thompson MM,van Bockxm

    更新日期：2011-11-11 00:00:00

  • Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection.

    abstract：:The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2011.07.025

    authors： Bhatia G,Patterson N,Pasaniuc B,Zaitlen N,Genovese G,Pollack S,Mallick S,Myers S,Tandon A,Spencer C,Palmer CD,Adeyemo AA,Akylbekova EL,Cupples LA,Divers J,Fornage M,Kao WH,Lange L,Li M,Musani S,Mychaleckyj JC,Og

    更新日期：2011-09-09 00:00:00

  • Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA.

    abstract：:Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic disorders characterized by abnormal iron deposition in the basal ganglia. We report that de novo mutations in WDR45, a gene located at Xp11.23 and encoding a beta-propeller scaffold protein with a putative role in autophagy, cause a distinctiv...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2012.10.019

    authors： Haack TB,Hogarth P,Kruer MC,Gregory A,Wieland T,Schwarzmayr T,Graf E,Sanford L,Meyer E,Kara E,Cuno SM,Harik SI,Dandu VH,Nardocci N,Zorzi G,Dunaway T,Tarnopolsky M,Skinner S,Frucht S,Hanspal E,Schrander-Stumpel C,

    更新日期：2012-12-07 00:00:00

  • The spreading of X inactivation into autosomal material of an x;autosome translocation: evidence for a difference between autosomal and X-chromosomal DNA.

    abstract：:X inactivation involves initiation, propagation, and maintenance of genetic inactivation. Studies of replication timing in X;autosome translocations have suggested that X inactivation may spread into adjacent autosomal DNA. To examine the inactivation of autosomal material at the molecular level, we assessed the trans...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/301922

    authors： White WM,Willard HF,Van Dyke DL,Wolff DJ

    更新日期：1998-07-01 00:00:00

  • Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p.

    abstract：:Restless legs syndrome (RLS) is a common neurological disorder that affects 5%-12% of all whites. To genetically dissect this complex disease, we characterized 15 large and extended multiplex pedigrees, consisting of 453 subjects (134 affected with RLS). A familial aggregation analysis was performed, and SAGE FCOR was...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/420772

    authors： Chen S,Ondo WG,Rao S,Li L,Chen Q,Wang Q

    更新日期：2004-05-01 00:00:00

  • Characterization of the patterns of polymorphism in a "cryptic repeat" reveals a novel type of hypervariable sequence.

    abstract：:Alternating purine and pyrimidine repeats (RY(i)) are an abundant source of polymorphism. The subset with long tandem repeats of GT or AC (GT(i)) have been studied extensively, but cryptic RY(i) (i.e., no single tandem repeat predominates) have received little attention. The factor IX gene has a polymorphic cryptic RY...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Jacobson DP,Schmeling P,Sommer SS

    更新日期：1993-08-01 00:00:00

  • Electrotypes and formal genetics of red cell glutathione peroxidase (GPX1) in the Djuka of Surinam.

    abstract：:Samples of venous blood from 239 male and 476 female adults including 41 pairs of parents and 123 of their children belonging to a Surinam population called the Djuka or Bush Negroes of West African origin were screened for electrophoretic variants of red cell glutathione peroxidase (GPX1) in Cellogel. The results con...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Meera Khan P,Verma C,Wijnen LM,Wijnen JT,Prins HK,Nijenhuis LE

    更新日期：1986-05-01 00:00:00

  • Distinct mutations in the receptor tyrosine kinase gene ROR2 cause brachydactyly type B.

    abstract：:Brachydactyly type B (BDB) is an autosomal dominant skeletal disorder characterized by hypoplasia/aplasia of distal phalanges and nails. Recently, heterozygous mutations of the orphan receptor tyrosine kinase (TK) ROR2, located within a distinct segment directly after the TK domain, have been shown to be responsible f...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/303084

    authors： Schwabe GC,Tinschert S,Buschow C,Meinecke P,Wolff G,Gillessen-Kaesbach G,Oldridge M,Wilkie AO,Kömec R,Mundlos S

    更新日期：2000-10-01 00:00:00

  • The ancestry of Brazilian mtDNA lineages.

    abstract：:We have analyzed 247 Brazilian mtDNAs for hypervariable segment (HVS)-I and selected restriction fragment-length-polymorphism sites, to assess their ancestry in different continents. The total sample showed nearly equal amounts of Native American, African, and European matrilineal genetic contribution but with regiona...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/303004

    authors： Alves-Silva J,da Silva Santos M,Guimarães PE,Ferreira AC,Bandelt HJ,Pena SD,Prado VF

    更新日期：2000-08-01 00:00:00

  • Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p.

    abstract：:Systemic lupus erythematosus is a prototypic autoimmune disease. Apart from rare monogenic deficiencies of complement factors, where lupuslike disease may occur in association with other autoimmune diseases or high susceptibility to bacterial infections, its etiology is multifactorial in nature. Cutaneous findings are...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/507848

    authors： Lee-Kirsch MA,Gong M,Schulz H,Rüschendorf F,Stein A,Pfeiffer C,Ballarini A,Gahr M,Hubner N,Linné M

    更新日期：2006-10-01 00:00:00

  • Gyrate atrophy of the choroid and retina: characterization of mutant ornithine aminotransferase and mechanism of response to vitamin B6.

    abstract：:The purpose of this study was to characterize the mutant enzyme in nine patients with gyrate atrophy of the choroid and retina associated with ornithine aminotransferase (OAT) deficiency, to elucidate the mechanism of response to pyridoxine in four pyridoxine-responsive patients, and to determine the extent of genetic...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Kennaway NG,Stankova L,Wirtz MK,Weleber RG

    更新日期：1989-03-01 00:00:00

  • Argininosuccinate lyase deficiency: evidence for heterogeneous structural gene mutations by immunoblotting.

    abstract：:Argininosuccinate lyase (AS lyase) deficiency is an inborn error of the urea cycle with extensive clinical and genetic heterogeneity. We investigated the biochemical basis of the enzyme defect and the genetic heterogeneity in this disorder using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Simard L,O'Brien WE,McInnes RR

    更新日期：1986-07-01 00:00:00

  • Trisomy 21: association between reduced recombination and nondisjunction.

    abstract：:To assess the association between recombination and nondisjunction of chromosome 21, we analyzed cytogenetic and DNA markers in 104 trisomy 21 individuals and their parents. Our DNA marker studies of parental origin were informative in 100 cases, with the overwhelming majority (94) being maternal in origin. This value...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Sherman SL,Takaesu N,Freeman SB,Grantham M,Phillips C,Blackston RD,Jacobs PA,Cockwell AE,Freeman V,Uchida I

    更新日期：1991-09-01 00:00:00

  • A test of the hypothesis that age at onset in Huntington disease is controlled by an X-linked recessive modifier.

    abstract：:Data from the Research Roster for Huntington Disease Patients and Families were used to assess the hypothesis that juvenile onset in Huntington disease is determined by an X-linked recessive modifying gene in the affected parent. The observed proportion of affected fathers to affected mothers who had such offspring w...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Ridley RM,Farrer LA,Frith CD,Conneally PM

    更新日期：1992-03-01 00:00:00

  • Familial deafness, congenital heart defects, and posterior embryotoxon caused by cysteine substitution in the first epidermal-growth-factor-like domain of jagged 1.

    abstract：:In the present study, we report a kindred with hearing loss, congenital heart defects, and posterior embryotoxon, segregating as autosomal dominant traits. Six of seven available affected patients manifested mild-to-severe combined hearing loss, predominantly affecting middle frequencies. Two patients were diagnosed w...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/341327

    authors： Le Caignec C,Lefevre M,Schott JJ,Chaventre A,Gayet M,Calais C,Moisan JP

    更新日期：2002-07-01 00:00:00

  • Analysis of deoxyribonucleic acid replication in human X chromosomes by fluorescence microscopy.

    abstract：:The genetically inactive, late-replicating human female X chromosome can be effectively distinguished from its more active, earlier-replicating homologue, when cells are grown according to the appropriate BrdU-33258 Hoechst protocol. Results obtained from a fluorescence analysis of DNA replication in X chromosomes are...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Willard HF,Latt SA

    更新日期：1976-05-01 00:00:00

  • Mismatches in genetic markers in a large family study.

    abstract：:The Hawaii Family Study of Cognition provided an opportunity to investigate the frequency and implications of non-agreement, or mismatches, between observed and expected genetic marker phenotypes of husbands, wives, and children. Mismatch data from 68 families in which one or both spouses were known not to be a biolog...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Ashton GC

    更新日期：1980-07-01 00:00:00

  • Management of Secondary Genomic Findings.

    abstract：:Secondary genomic findings are increasingly being returned to individuals as opportunistic screening results. A secondary finding offers the chance to identify and mitigate disease that may otherwise be unrecognized in an individual. As a form of screening, secondary findings must be considered differently from sequen...

    journal_title：American journal of human genetics

    pub_type： 杂志文章,评审

    doi：10.1016/j.ajhg.2020.05.002

    authors： Katz AE,Nussbaum RL,Solomon BD,Rehm HL,Williams MS,Biesecker LG

    更新日期：2020-07-02 00:00:00

  • Evidence for the close linkage between lymphocyte cytosol polypeptide with molecular weight of 64,000 (LCP1) and esterase D.

    abstract：:The genetic linkage of the loci for lymphocyte cytosol polypeptide with molecular weight of 64,000 (LCP1) and esterase (ESD) were examined by two-dimensional gel electrophoresis using blood from four informative families. No recombinants were observed in the four families totaling 17 children, giving a summed lod scor...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Kondo I,Hamaguchi H

    更新日期：1985-11-01 00:00:00

  • Quantitative-trait homozygosity and association mapping and empirical genomewide significance in large, complex pedigrees: fasting serum-insulin level in the Hutterites.

    abstract：:We present methods for linkage and association mapping of quantitative traits for a founder population with a large, known genealogy. We detect linkage to quantitative-trait loci (QTLs) through a multipoint homozygosity-mapping method. We propose two association methods, one of which is single point and uses a general...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/339705

    authors： Abney M,Ober C,McPeek MS

    更新日期：2002-04-01 00:00:00

  • DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis.

    abstract：:Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unk...

    journal_title：American journal of human genetics

    pub_type： 杂志文章,meta分析

    doi：10.1016/j.ajhg.2016.02.019

    authors： Joubert BR,Felix JF,Yousefi P,Bakulski KM,Just AC,Breton C,Reese SE,Markunas CA,Richmond RC,Xu CJ,Küpers LK,Oh SS,Hoyo C,Gruzieva O,Söderhäll C,Salas LA,Baïz N,Zhang H,Lepeule J,Ruiz C,Ligthart S,Wang T,Taylor

    更新日期：2016-04-07 00:00:00

  • Targeting Dyrk1A with AAVshRNA attenuates motor alterations in TgDyrk1A, a mouse model of Down syndrome.

    abstract：:Genetic-dissection studies carried out with Down syndrome (DS) murine models point to the critical contribution of Dyrk1A overexpression to the motor abnormalities and cognitive deficits displayed in DS individuals. In the present study we have used a murine model overexpressing Dyrk1A (TgDyrk1A mice) to evaluate whet...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2008.09.010

    authors： Ortiz-Abalia J,Sahún I,Altafaj X,Andreu N,Estivill X,Dierssen M,Fillat C

    更新日期：2008-10-01 00:00:00

  • An alternate method for demonstration of bisphosphoglyceromutase (DPGM) on starch gels.

    abstract：:The phosphatase activity of bisphosphoglyceromutase (DPGM) was used to determine the phenotypes of the enzyme. DPGM was polymorphic in four Alaskan ethnic groups. ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Scott EM,Wright RC

    更新日期：1982-11-01 00:00:00

  • Contrasting evolutionary histories among tightly linked HLA loci.

    abstract：:Genes comprising the major histocompatibility complex (MHC) play a central role in governing the immune response of vertebrates. A great deal of information has been revealed on the molecular biology and physiology of these loci, but three features-the high polymorphism, tight linkage among the loci, and the nonrandom...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Klitz W,Thomson G,Baur MP

    更新日期：1986-09-01 00:00:00

  • Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation.

    abstract：:Patients with Joubert syndrome 2 (JBTS2) suffer from a neurological disease manifested by psychomotor retardation, hypotonia, ataxia, nystagmus, and oculomotor apraxia and variably associated with dysmorphism, as well as retinal and renal involvement. Brain MRI results show cerebellar vermis hypoplasia and additional ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2009.12.007

    authors： Edvardson S,Shaag A,Zenvirt S,Erlich Y,Hannon GJ,Shanske AL,Gomori JM,Ekstein J,Elpeleg O

    更新日期：2010-01-01 00:00:00