A5044187125- Down syndrome and intellectual disability research
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Hedgehog Signaling Pathway Studies
- Prenatal Screening and Diagnostics
- Neurogenesis and neuroplasticity mechanisms
- Cleft Lip and Palate Research
- Fetal and Pediatric Neurological Disorders
- Alzheimer's disease research and treatments
- Cardiovascular Function and Risk Factors
- Alcoholism and Thiamine Deficiency
- Epigenetics and DNA Methylation
- Vitamin C and Antioxidants Research
- Biochemical Acid Research Studies
Johns Hopkins University
2010-2023
Johns Hopkins Medicine
2010-2020
Animal models of Down syndrome (DS), trisomic for human chromosome 21 (HSA21) genes or orthologs, provide insights into better understanding and treatment options. The only existing transchromosomic (Tc) mouse DS model, Tc1, carries a HSA21 with over 50 protein coding (PCGs) disrupted. Tc1 is mosaic, compromising interpretation results. Here, we “clone” the 34 MB long arm (HSA21q) as artificial (MAC). Through multiple steps microcell-mediated transfer, created new Tc Tc(HSA21q;MAC)1Yakaz...
α-lipoic acid (LA) is an essential cofactor for mitochondrial dehydrogenases and required cell growth, metabolic fuel production, antioxidant defense. In vitro, LA binds copper (Cu) with high affinity as endogenous membrane permeable metabolite could be advantageous in mitigating the consequences of Cu overload human diseases. We tested this hypothesis 3T3-L1 preadipocytes inactivated transporter Atp7a; these cells accumulate show morphologic changes mitochondria impairment. Treatment...
Humans with Down syndrome (DS) and Ts65Dn mice both show a reduced volume of the cerebellum due to significant reduction in density granule neurons. Recently, cerebellar hypoplasia was rescued by single treatment SAG, an agonist Sonic hedgehog pathway, administered on day birth. In addition normalizing morphology, this restored ability learn spatial navigation task, which is associated hippocampal function. It not clear what extent improved performance results from restoration architecture...
The Ts65Dn mouse is trisomic for orthologs of about half the genes on Hsa21. A number phenotypes in these mice parallel those humans with trisomy 21 (Down syndrome), including cognitive deficits due to hippocampal malfunction that are sufficiently similar human "therapies" developed making their way clinical trials. However, impact model limited by availability. cannot be completely inbred and males generally considered sterile. Females have few, small litters they exhibit poor care...
Hedgehog (HH) signaling, and particularly signaling by sonic hedgehog (SHH), is implicated in several essential activities during morphogenesis, its misexpression causes a number of developmental disorders humans. In particular, reduced mitogenic response cerebellar granule cell precursors to SHH mouse model for Down syndrome (DS), Ts65Dn, substantially responsible size. A single treatment newborn trisomic mice with an agonist the pathway (SAG) normalizes morphology restores some cognitive...
Down syndrome (DS) is the leading genetic cause of intellectual disability and causes early-onset dementia cerebellar hypoplasia. The prevalence attention deficit hyperactivity disorder elevated in children with DS. aneuploid DS mouse model "Ts65Dn" shows prominent brain phenotypes, including learning memory deficits, hypoplasia, locomotor hyperactivity. Previous studies indicate that impaired Sonic hedgehog (Shh) signaling contributes to neurological phenotypes associated neurodegenerative...
Down syndrome (DS), a genetic disorder caused by partial or complete triplication of chromosome 21, is the most common cause intellectual disability. DS mouse models and cell lines display defects in cellular adaptive stress responses including autophagy, unfolded protein response, mitochondrial bioenergetics. We tested ability hydroxyurea (HU), an FDA-approved pharmacological agent that activates response pathways, to improve cognitive function Ts65Dn mice. The chronic HU treatment started...
Abstract Down syndrome (DS) is a complex human condition, and animal models trisomic for chromosome 21 (HSA21) genes or orthologs provide insights into better understanding treating DS. However, HSA21 are distributed three mouse chromosomes, preventing us from generating trisomy of complete set orthologs. The only existing humanized DS model, Tc1, carries with over 20% protein coding (PCGs) disrupted. More importantly, due to the centromere, Tc1 mosaic (a mix euploid cells), which makes...
Summary People with Down syndrome (DS) have intellectual disability, early-onset dementia, and cerebellar hypoplasia. Trisomic granule cell precursors from Ts65Dn, a mouse model of DS, had deficit in mitogenic response to Sonic hedgehog (Shh) vitro , newborn Ts65Dn mice received single subcutaneous injection the Shh signaling agonist SAG normalized morphology improved spatial learning hippocampal synaptic plasticity at adult. However, cognitive effects overexpression vivo where acts improve...