CoChat
Sign Up
Cited by 11Down syndrome and intellectual disability researchGenetics and Neurodevelopmental DisordersAlzheimer's disease research and treatments

Sexually dimorphic DYRK1A overexpression on postnatal day 15 in the Ts65Dn mouse model of down syndrome: effects of pharmacological targeting on behavioral phenotypes

Open access
Hawley, Laura E., Prochaska, Faith, Stringer, Megan, Goodlett, Charles R., Roper, Randall J.·2022·Pharmacology Biochemistry and Behavior
DOI 10.1016/j.pbb.2022.173404PMC PMC9516663
Open this paper in CoChat — free account

Abstract

The neurotypical spatiotemporal patterns of gene expression are disrupted in Down syndrome (DS) by trisomy of human chromosome 21 (Hsa21), resulting in altered behavioral development and brain circuitry. The Ts65Dn DS mouse model exhibits similar phenotypes to individuals with DS due to three copies of approximately one-half of the genes found on Hsa21. Dual-specificity Tyrosine Phosphorylation-regulated Kinase 1a (Dyrk1a), one of these triplicated genes, is an attractive target to normalize brain development due to its influence in cellular brain deficits seen in DS. We hypothesized that postnatal development of DYRK1A expression is dysregulated in trisomic animals, and found significant overexpression of DYRK1A in the hippocampus, cerebral cortex, and cerebellum at postnatal day (P) 15 in male-but not female-Ts65Dn mice. We then hypothesized the existence of sex-dependent effects of trisomy on neurobehavioral attributes during P16-17, and that administration of a DYRK1A inhibitor (CX-4945, ~75 mg/kg) beginning on P14 would normalize aberrant behavior in trisomic animals. Both male and female trisomic mice given control injections of phosphate buffered saline (PBS) displayed sustained levels of locomotor activity over a 10-minute test in contrast to the PBS-treated euploid animals that showed significant within-session habituation. Trisomic animals were more persistent in choosing to remain in home shavings in a preference test. Treatment with CX-4945 failed to confirm therapeutic effects. CX-4945 prevented growth, and both CX-4945 and its 10% dimethyl sulfoxide vehicle affected locomotor activity in trisomic and euploid groups, indicating a non-specific disruption of behavior. Despite the negative outcomes for CX-4945, the novel demonstration of sexually dimorphic DYRK1A expression in trisomic animals at P15 supports the broader hypothesis that overexpression of trisomic genes in DS can vary with age, sex, and brain region. Identifying the developmental timing of periods of dysregulated DYRK1A may be important for understanding individual differences in neurodevelopmental trajectories in DS and for developing effective therapeutic interventions targeting DYRK1A.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.pbb.2022.173404

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • DYRK1A was elevated in P15 Ts65Dn male but not female mice.

    “Furthermore, we recently showed that DYRK1A was elevated in P15 Ts65Dn male but not female mice (Hawley et al., 2022).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Hawley et al., 2022

  • At P15, DYRK1A was significantly overexpressed in the hippocampus, cerebral cortex, and cerebellum of male Ts65Dn mice compared to euploid littermate controls; expression in P15 females was not significantly higher in any brain region tested.

    “At P15, DYRK1A was significantly overexpressed in the hippocampus, cerebral cortex, and cerebellum of male Ts65Dn mice compared to euploid littermate controls; expression in P15 females was not significantly higher in any brain region tested (Hawley et al., 2022).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Hawley et al., 2022

  • The new data show that similar sex differences extended to P18 (except for cerebral cortex), P21, and P24, implicating important sex differences in DYRK1A levels in Ts65Dn mice that emerge during the third postnatal week.

    “The P15 data were included in our previous report (Hawley et al., 2022), and the new data show that similar sex differences extended to P18 (except for cerebral cortex), P21, and P24, implicating important sex differences in DYRK1A levels in Ts65Dn mice that emerge during the third postnatal week.”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Hawley et al., 2022

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 84 · Cited by 11

Research works printed but not linked: 79

  1. Ahn KJ, Jeong HK, Choi HS, Ryoo SR, Kim YJ, 2006 DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects. Neurobiol Dis 22: 463– 472. 16455265
  2. Alam El-Deen N, Alwakeel AA, El-Gilany AH and Wahba Y, 2021 Burden of family caregivers of Down syndrome children: a cross-sectional study. Fam Pract 38: 160– 165. 33011802
  3. Aldridge GM, Podrebarac DM, Greenough WT and Weiler IJ, 2008 The use of total protein stains as loading controls: an alternative to high-abundance single-protein controls in semi-quantitative immunoblotting. J Neurosci Methods 172: 250– 254. 18571732 PMC2567873
  4. Altafaj X, Dierssen M, Baamonde C, Marti E, Visa J, 2001 Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down’s syndrome. Hum Mol Genet 10: 1915– 1923. 11555628
  5. Aoki S, Yamauchi Y and Hashimoto K, 2018 Developmental trend of children with Down’s syndrome - How do sex and neonatal conditions influence their developmental patterns? Brain Dev 40: 181– 187. 29054333
  6. Barros ALO, Barros AO, Barros GLM and Santos M, 2017 Burden of caregivers of children and adolescents with Down Syndrome. Cien Saude Colet 22: 3625– 3634. 29211168
  7. Baxter LL, Moran TH, Richtsmeier JT, Troncoso J and Reeves RH, 2000 Discovery and genetic localization of Down syndrome cerebellar phenotypes using the Ts65Dn mouse. Hum Mol Genet 9: 195– 202. 10607830
  8. Belichenko NP, Belichenko PV, Kleschevnikov AM, Salehi A, Reeves RH, 2009 The “Down syndrome critical region” is sufficient in the mouse model to confer behavioral, neurophysiological, and synaptic phenotypes characteristic of Down syndrome. J Neurosci 29: 5938– 5948. 19420260 PMC3849469
  9. Block A, Ahmed MM, Dhanasekaran AR, Tong S and Gardiner KJ, 2015 Sex differences in protein expression in the mouse brain and their perturbations in a model of Down syndrome. Biol Sex Differ 6: 24. 26557979 PMC4640233
  10. Block A, Ahmed MM, Rueda N, Hernandez MC, Martinez-Cue C, 2018 The GABAAalpha5-selective Modulator, RO4938581, Rescues Protein Anomalies in the Ts65Dn Mouse Model of Down Syndrome. Neuroscience 372: 192– 212. 29292072
  11. Bradford MM, 1976 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical biochemistry 72: 248– 254. 942051
  12. Brayton CF, 1986 Dimethyl sulfoxide (DMSO): a review. Cornell Vet 76: 61– 90. 3510103
  13. Bygrave AM, Jahans-Price T, Wolff AR, Sprengel R, Kullmann DM, 2019 Hippocampal-prefrontal coherence mediates working memory and selective attention at distinct frequency bands and provides a causal link between schizophrenia and its risk gene GRIA1. Transl Psychiatry 9: 142. 31000699 PMC6472369
  14. Castellanos FX, and Tannock R, 2002 Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nat Rev Neurosci 3: 617– 628. 12154363
  15. Chakrabarti L, Best TK, Cramer NP, Carney RS, Isaac JT, 2010 Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome. Nat Neurosci 13: 927– 934. 20639873 PMC3249618
  16. Channell MM, Hahn LJ, Rosser TC, Hamilton D, Frank-Crawford MA, 2019 Characteristics Associated with Autism Spectrum Disorder Risk in Individuals with Down Syndrome. J Autism Dev Disord 49: 3543– 3556. 31124029
  17. Chen JY, Lin JR, Tsai FC and Meyer T, 2013 Dosage of Dyrk1a shifts cells within a p21-cyclin D1 signaling map to control the decision to enter the cell cycle. Mol Cell 52: 87– 100. 24119401 PMC4039290
  18. Coussons-Read ME, and Crnic LS, 1996 Behavioral assessment of the Ts65Dn mouse, a model for Down syndrome: altered behavior in the elevated plus maze and open field. Behav Genet 26: 7– 13. 8852727
  19. Cuzon VC, Yeh PW, Yanagawa Y, Obata K and Yeh HH, 2008 Ethanol consumption during early pregnancy alters the disposition of tangentially migrating GABAergic interneurons in the fetal cortex. J Neurosci 28: 1854– 1864. 18287502 PMC6671430
  20. Das I, Park JM, Shin JH, Jeon SK, Lorenzi H, 2013 Hedgehog agonist therapy corrects structural and cognitive deficits in a down syndrome mouse model. Sci Transl Med 5: 201ra120. PMC4006719 24005160
  21. De la Torre R, De Sola S, Pons M, Duchon A, de Lagran MM, 2014 Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans. Mol Nutr Food Res 58: 278– 288. 24039182
  22. De la Torre R, and Dierssen M, 2012 Therapeutic approaches in the improvement of cognitive performance in Down syndrome: past, present, and future. Prog Brain Res 197: 1– 14. 22541285
  23. Demas GE, Nelson RJ, Krueger BK and Yarowsky PJ, 1996 Spatial memory deficits in segmental trisomic Ts65Dn mice. Behav Brain Res 82: 85– 92. 9021073
  24. Doischer D, Hosp JA, Yanagawa Y, Obata K, Jonas P, 2008 Postnatal differentiation of basket cells from slow to fast signaling devices. J Neurosci 28: 12956– 12968. 19036989 PMC6671784
  25. Eaton SL, Roche SL, Llavero Hurtado M, Oldknow KJ, Farquharson C, 2013 Total protein analysis as a reliable loading control for quantitative fluorescent Western blotting. PLoS One 8: e72457. PMC3758299 24023619
  26. Escorihuela RM, Fernandez-Teruel A, Vallina IF, Baamonde C, Lumbreras MA, 1995 A behavioral assessment of Ts65Dn mice: a putative Down syndrome model. Neurosci Lett 199: 143– 146. 8584244
  27. Faizi M, Bader PL, Tun C, Encarnacion A, Kleschevnikov A, 2011 Comprehensive behavioral phenotyping of Ts65Dn mouse model of Down syndrome: activation of beta1-adrenergic receptor by xamoterol as a potential cognitive enhancer. Neurobiol Dis 43: 397– 413. 21527343 PMC3539757
  28. Ferguson AD, Sheth PR, Basso AD, Paliwal S, Gray K, 2011 Structural basis of CX-4945 binding to human protein kinase CK2. FEBS Lett 585: 104– 110. 21093442
  29. Fernández-Martínez P, Zahonero C and Sánchez-Gómez P, 2015 DYRK1A: the double-edged kinase as a protagonist in cell growth and tumorigenesis. Molecular & Cellular Oncology 2: e970048. PMC4905233 27308401
  30. Fortress AM, Hamlett ED, Vazey EM, Aston-Jones G, Cass WA, 2015 Designer receptors enhance memory in a mouse model of Down syndrome. J Neurosci 35: 1343– 1353. 25632113 PMC4308587
  31. Gao FJ, Klinedinst D, Fernandez FX, Cheng B, Savonenko A, 2021 Forebrain Shh overexpression improves cognitive function and locomotor hyperactivity in an aneuploid mouse model of Down syndrome and its euploid littermates. Acta Neuropathol Commun 9: 137. 34399854 PMC8365939
  32. Gardiner KJ, 2015 Pharmacological approaches to improving cognitive function in Down syndrome: current status and considerations. Drug Des Devel Ther 9: 103– 125. PMC4277121 25552901
  33. Geelhoed EA, Bebbington A, Bower C, Deshpande A and Leonard H, 2011 Direct health care costs of children and adolescents with Down syndrome. J Pediatr 159: 541– 545. 21784457 PMC3858577
  34. Godfrey M, and Lee NR, 2018 Memory profiles in Down syndrome across development: a review of memory abilities through the lifespan. J Neurodev Disord 10: 5. 29378508 PMC5789527
  35. Goodlett CR, Stringer M, LaCombe J, Patel R, Wallace JM, 2020 Evaluation of the therapeutic potential of Epigallocatechin-3-gallate (EGCG) via oral gavage in young adult Down syndrome mice. Sci Rep 10: 10426. 32591597 PMC7319987
  36. Guidi S, Ciani E, Bonasoni P, Santini D and Bartesaghi R, 2011 Widespread proliferation impairment and hypocellularity in the cerebellum of fetuses with down syndrome. Brain Pathol 21: 361– 373. 21040072 PMC8094247
  37. Hanslick JL, Lau K, Noguchi KK, Olney JW, Zorumski CF, 2009 Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system. Neurobiol Dis 34: 1– 10. 19100327 PMC2682536
  38. Haydar TF, and Reeves RH, 2012 Trisomy 21 and early brain development. Trends Neurosci 35: 81– 91. 22169531 PMC3273608
  39. Holtzman DM, Santucci D, Kilbridge J, Chua-Couzens J, Fontana DJ, 1996 Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proc Natl Acad Sci U S A 93: 13333– 13338. 8917591 PMC24093
  40. Kim H, Lee KS, Kim AK, Choi M, Choi K, 2016 A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition. Dis Model Mech 9: 839– 848. 27483355 PMC5007978
  41. Kleschevnikov AM, Belichenko PV, Gall J, George L, Nosheny R, 2012 Increased efficiency of the GABAA and GABAB receptor-mediated neurotransmission in the Ts65Dn mouse model of Down syndrome. Neurobiol Dis 45: 683– 691. 22062771 PMC3259223
  42. LaCombe JM, and Roper RJ, 2020 Skeletal dynamics of Down syndrome: A developing perspective. Bone 133: 115215. PMC7044033 31887437
  43. Laviola G, and Alleva E, 1990 Ontogeny of muscimol effects on locomotor activity, habituation, and pain reactivity in mice. Psychopharmacology (Berl) 102: 41– 48. 2392506
  44. Martinez-Cue C, Baamonde C, Lumbreras M, Paz J, Davisson MT, 2002 Differential effects of environmental enrichment on behavior and learning of male and female Ts65Dn mice, a model for Down syndrome. Behav Brain Res 134: 185– 200. 12191805
  45. Martinez-Cue C, Rueda N, Garcia E and Florez J, 2006 Anxiety and panic responses to a predator in male and female Ts65Dn mice, a model for Down syndrome. Genes Brain Behav 5: 413– 422. 16879635
  46. McFarlane L, Truong V, Palmer JS and Wilhelm D, 2013 Novel PCR assay for determining the genetic sex of mice. Sex Dev 7: 207– 211. 23571295
  47. Mitra A, Blank M and Madison DV, 2012 Developmentally altered inhibition in Ts65Dn, a mouse model of Down syndrome. Brain Res 1440: 1– 8. 22284618 PMC4114405
  48. Moldrich RX, Dauphinot L, Laffaire J, Rossier J and Potier MC, 2007 Down syndrome gene dosage imbalance on cerebellum development. Prog Neurobiol 82: 87– 94. 17408845
  49. Murphy JM, Meeker RB, Porada KJ and Nagy ZM, 1979 GABA-mediated behavioral inhibition during ontogeny in the mouse. Psychopharmacology (Berl) 64: 237– 242. 115048
  50. Nagy ZM, Murphy JM and Ray D, 1975 Development of behavioral arousal and inhibition in the Swiss-Webster mouse. Bulletin of the Psychonomic Society 6: 146– 148.
  51. Nagy ZM, and Ritter M, 1976 Ontogeny of behavioral arousal in the mouse: Effect of prior testing upon age of peak activity. Bulletin of the Psychonomic Society 7: 285– 288.
  52. Nguyen TL, Fruit C, Herault Y, Meijer L and Besson T, 2017 Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors: a survey of recent patent literature. Expert Opin Ther Pat 27: 1183– 1199. 28766366
  53. Nie X, Li C, Hu S, Xue F, Kang YJ, 2017 An appropriate loading control for western blot analysis in animal models of myocardial ischemic infarction. Biochem Biophys Rep 12: 108– 113. 28955798 PMC5613232
  54. Olmos-Serrano JL, Tyler WA, Cabral HJ and Haydar TF, 2016 Longitudinal measures of cognition in the Ts65Dn mouse: Refining windows and defining modalities for therapeutic intervention in Down syndrome. Exp Neurol 279: 40– 56. 26854932 PMC5716476
  55. Park J, and Chung KC, 2013 New Perspectives of Dyrk1A Role in Neurogenesis and Neuropathologic Features of Down Syndrome. Exp Neurobiol 22: 244– 248. 24465139 PMC3897685
  56. Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, 2010 Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004–2006. Birth Defects Res A Clin Mol Teratol 88: 1008– 1016. 20878909
  57. Parrini M, Naskar S, Alberti M, Colombi I, Morelli G, 2021 Restoring neuronal chloride homeostasis with anti-NKCC1 gene therapy rescues cognitive deficits in a mouse model of Down syndrome. Mol Ther 29: 3072– 3092. 34058387 PMC8531145
  58. Prut L, and Belzung C, 2003 The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 463: 3– 33. 12600700
  59. Ray D, and Nagy ZM, 1978 Emerging cholinergic mechanisms and ontogeny of response inhibition in the mouse. J Comp Physiol Psychol 92: 335– 349. 670457
  60. Reeves RH, Irving NG, Moran TH, Wohn A, Kitt C, 1995 A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet 11: 177– 184. 7550346
  61. Reinholdt LG, Ding Y, Gilbert GJ, Czechanski A, Solzak JP, 2011 Molecular characterization of the translocation breakpoints in the Down syndrome mouse model Ts65Dn. Mamm Genome 22: 685– 691. 21953412 PMC3505986
  62. Richtsmeier JT, Baxter LL and Reeves RH, 2000 Parallels of craniofacial maldevelopment in Down syndrome and Ts65Dn mice. Dev Dyn 217: 137– 145. 10706138
  63. Roper RJ, St John HK, Philip J, Lawler A and Reeves RH, 2006 Perinatal loss of Ts65Dn Down syndrome mice. Genetics 172: 437– 443. 16172497 PMC1456171
  64. Saran NG, Pletcher MT, Natale JE, Cheng Y and Reeves RH, 2003 Global disruption of the cerebellar transcriptome in a Down syndrome mouse model. Hum Mol Genet 12: 2013– 2019. 12913072
  65. Sitz JH, Tigges M, Baumgärtel K, Khaspekov LG and Lutz B, 2004 Dyrk1A potentiates steroid hormone-induced transcription via the chromatin remodeling factor Arip4. Mol Cell Biol 24: 5821– 5834. 15199138 PMC480880
  66. Souchet B, Guedj F, Sahun I, Duchon A, Daubigney F, 2014 Excitation/inhibition balance and learning are modified by Dyrk1a gene dosage. Neurobiol Dis 69: 65– 75. 24801365
  67. Stewart LS, Persinger MA, Cortez MA and Snead OC 3rd, 2007 Chronobiometry of behavioral activity in the Ts65Dn model of Down syndrome. Behav Genet 37: 388– 398. 17146725
  68. Stringer M, Abeysekera I, Thomas J, LaCombe J, Stancombe K, 2017a Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes. Physiol Behav 177: 230– 241. 28478033 PMC5525541
  69. Stringer M, Goodlett CR and Roper RJ, 2017b Targeting trisomic treatments: optimizing Dyrk1a inhibition to improve Down syndrome deficits. Mol Genet Genomic Med 5: 451– 465. 28944229 PMC5606891
  70. Thomas JR, LaCombe J, Long R, Lana-Elola E, Watson-Scales S, 2020 Interaction of sexual dimorphism and gene dosage imbalance in skeletal deficits associated with Down syndrome. Bone 136: 115367. PMC7262595 32305495
  71. Thompson BJ, Bhansali R, Diebold L, Cook DE, Stolzenburg L, 2015 DYRK1A controls the transition from proliferation to quiescence during lymphoid development by destabilizing Cyclin D3. J Exp Med 212: 953– 970. 26008897 PMC4451127
  72. Tucker LB, and McCabe JT, 2021 Measuring Anxiety-Like Behaviors in Rodent Models of Traumatic Brain Injury. Front Behav Neurosci 15: 682935. PMC8586518 34776887
  73. Velazquez R, Meechoovet B, Ow A, Foley C, Shaw A, 2019 Chronic Dyrk1 Inhibition Delays the Onset of AD-Like Pathology in 3xTg-AD Mice. Mol Neurobiol 56: 8364– 8375. 31240602
  74. Vidal V, Garcia-Cerro S, Martinez P, Corrales A, Lantigua S, 2018 Decreasing the Expression of GABAA alpha5 Subunit-Containing Receptors Partially Improves Cognitive, Electrophysiological, and Morphological Hippocampal Defects in the Ts65Dn Model of Down Syndrome. Mol Neurobiol 55: 4745– 4762. 28717969
  75. Welinder C, and Ekblad L, 2011 Coomassie staining as loading control in Western blot analysis. J Proteome Res 10: 1416– 1419. 21186791
  76. Workman AD, Charvet CJ, Clancy B, Darlington RB and Finlay BL, 2013 Modeling transformations of neurodevelopmental sequences across mammalian species. J Neurosci 33: 7368– 7383. 23616543 PMC3928428
  77. Wyatt D, Parker KL, Kemp SF, Chiang J and Davis DA, 2010 The evaluation and followup of children referred to pediatric endocrinologists for short stature. Int J Pediatr Endocrinol 2010: 652013. PMC2905720 20652081
  78. Yabut O, Domogauer J and D’Arcangelo G, 2010 Dyrk1A overexpression inhibits proliferation and induces premature neuronal differentiation of neural progenitor cells. J Neurosci 30: 4004– 4014. 20237271 PMC3842457
  79. de San Martin Zorrilla, Donato J,C, Peixoto J, Aguirre A, Choudhary V, 2020 Alterations of specific cortical GABAergic circuits underlie abnormal network activity in a mouse model of Down syndrome. Elife 9. PMC7481006 32783810

Authors
Hawley, L. E., Prochaska, F., Stringer, M., Goodlett, C. R., & Roper, R. J.
Affiliations
Indiana University – Purdue University Indianapolis (US)
Corresponding author
Roper, Randall J.
ORCID
Venue
Pharmacology Biochemistry and Behavior
Publisher
Elsevier BV
Published
2022-06
Volume
217
Pages
173404
ISSN
0091-3057 (ISSN-L)
DOI
10.1016/j.pbb.2022.173404
PMC
PMC9516663
OpenAlex
W4280540259
Cited by
11
References
84
Citations by year
2026: 2 · 2024: 3 · 2023: 3 · 2022: 3
FWCI
1.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmacology Biochemistry and Behavior (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
  • National Institutes of Health (UL1TR001108)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR078663)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Down syndrome, Ts65Dn mouse model, DYRK1A, sex differences, postnatal brain development, gene overexpression, CX-4945, DYRK1A inhibitors, locomotor activity, neurobehavioral phenotype, hippocampus, cerebral cortex, cerebellum
MeSH terms
Animals, Disease Models, Animal, Down Syndrome, Female, Male, Mice, Transgenic, Phenotype, Trisomy, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review