scholarly journals Behavior Variability of a Conditional Gene Knockout Mouse as a Measure of Subtle Phenotypic Trait Expression. The Case of Mouse Executive Function Distortion

2017 ◽  
Author(s):  
Pavel Prosselkov ◽  
Qi Zhang ◽  
Hiromichi Goto ◽  
Denis Polygalov ◽  
Thomas J. McHugh ◽  
...  
Keyword(s):  
Executive Function ◽  
Environmental Changes ◽  
Gene Knockout ◽  
Phenotypic Trait ◽  
Memory And Attention ◽  
Task Learning ◽  
Vertebrate Brain ◽  
Excitatory Pathways ◽  
Gene Knockout Mouse ◽  
Specific Pair

ABSTRACTTask learning relies on brain executive function (EF), the construct of controlling and coordinating behavior under the everlasting flow of environmental changes. We have previously shown, that a complete knockout of a vertebrate brain-specific pair of gene paralogs (Ntng1/2) distorts the mouse EF, making behavior less predictable (more variable) via the affected working memory and attention (1). In the current study, conditionally targeting either serotonin transporter (5-HTT) or Emx1-expressing neurons, we show that the cell type-specific ablation of Ntng1 within the excitatory circuits of either cortex or thalamus does not have a profound impact on the EF but rather affects its certain modalities, i.e. impulsivity and/or selective attention, modulated by cognitive demand. Several mice of both conditional genotypes simultaneously occupy either top or bottom parameter-specific behavioral ranks, indicative of a subject-unique antagonistic either proficit or deficit of function within the same behavior. Employing genotype-attributable behavior variability as a phenotypic trait, we deduce, that Ntng1-parsed excitatory pathways contribute but do not fully reconstitute the attention-impulsivity phenotypes, associated with the mouse EF deficit. However, complete knockdown of Ntng1/2, and associated with it behavior variability, explains the deficit of executive function and task learning.

scholarly journals The Relationship of Psychiatric Symptoms with Performance-Based and Self-Reported Cognitive Function After Ischemic Stroke

2021 ◽  
pp. 1-13
Author(s):  
Elisabeth Kliem ◽  
Elise Gjestad ◽  
Truls Ryum ◽  
Alexander Olsen ◽  
Bente Thommessen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Executive Function ◽  
Depressive Symptoms ◽  
Cognitive Function ◽  
Psychiatric Symptoms ◽  
Post Stroke ◽  
Cognitive Difficulties ◽  
Memory And Attention ◽  
Relationship Of ◽  
The Relationship

Abstract Objective: Findings on the relationship of psychiatric symptoms with performance-based and self-reported cognitive function post-stroke are inconclusive. We aimed to (1) study the relation of depression and anxiety to performance-based cognitive function and (2) explore a broader spectrum of psychiatric symptoms and their association with performance-based versus self-reported cognitive function. Method: Individuals with supratentorial ischemic stroke performed neuropsychological examination 3 months after stroke. For primary analyses, composite scores for memory and attention/executive function were calculated based on selected neuropsychological tests, and the Hospital Anxiety and Depression Scale (HADS) was used. Psychiatric symptoms and self-reported cognitive function for secondary aims were assessed using the Symptom-Checklist-90 – Revised (SCL-90-R). Results: In a sample of 86 patients [mean (M) age: 64.6 ± 9.2; Mini-Mental State Examination (MMSE), 3–7 days post-stroke: M = 28.4 ± 1.7; National Institutes of Health Stroke Scale (NIHSS) after 3 months: M = 0.7 ± 1.6] depressive symptoms (HADS) were associated with poorer memory performance after controlling for age, sex, and education (p ≤ .01). In a subsample (n = 41; Age: M = 65.7 ± 8.1; MMSE: M = 28.4 ± 1.8; NIHSS: M = 1.0 ± 1.9), symptoms of phobic anxiety (SCL-90-R) were associated with poorer performance-based memory and attention/executive function, and symptoms of anxiety (SCL-90-R) with lower attention/executive function. Higher levels of self-reported cognitive difficulties were associated with higher scores in all psychiatric domains (p ≤ .05). Conclusion: Even in relatively well-functioning stroke patients, depressive symptoms are associated with poorer memory. The results also suggest that various psychiatric symptoms are more related to self-reported rather than to performance-based cognitive function. Screening for self-reported cognitive difficulties may not only help to identify patients with cognitive impairment, but also those who need psychological treatment.

scholarly journals Differential response to heat stress among evolutionary lineages of an aquatic invertebrate species complex

2018 ◽  
Vol 14 (11) ◽  
pp. 20180498 ◽  
Author(s):  
Sofia Paraskevopoulou ◽  
Ralph Tiedemann ◽  
Guntram Weithoff
Keyword(s):  
Heat Stress ◽  
Cryptic Species ◽  
Heat Tolerance ◽  
Species Complex ◽  
Environmental Changes ◽  
Integrative Taxonomy ◽  
Sensu Stricto ◽  
Apparent Temperature ◽  
Phenotypic Trait ◽  
Evolutionary Lineages

Under global warming scenarios, rising temperatures can constitute heat stress to which species may respond differentially. Within a described species, knowledge on cryptic diversity is of further relevance, as different lineages/cryptic species may respond differentially to environmental change. The Brachionus calyciflorus species complex (Rotifera), which was recently described using integrative taxonomy, is an essential component of aquatic ecosystems. Here, we tested the hypothesis that these (formerly cryptic) species differ in their heat tolerance. We assigned 47 clones with nuclear ITS1 (nuITS1) and mitochondrial COI (mtCOI) markers to evolutionary lineages, now named B. calyciflorus sensu stricto (s.s.) and B. fernandoi . We selected 15 representative clones and assessed their heat tolerance as a bi-dimensional phenotypic trait affected by both the intensity and duration of heat stress. We found two distinct groups, with B. calyciflorus s.s. clones having higher heat tolerance than the novel species B. fernandoi . This apparent temperature specialization among former cryptic species underscores the necessity of a sound species delimitation and assignment, when organismal responses to environmental changes are investigated.

Atrial Natriuretic Peptide: Regulator of Chronic Arterial Blood Pressure

Physiology ◽  
2000 ◽  
Vol 15 (3) ◽  
pp. 143-149 ◽  
Author(s):  
Luis Gabriel Melo ◽  
Stephen C. Pang ◽  
Uwe Ackermann
Keyword(s):  
Blood Pressure ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Salt Intake ◽  
Gene Knockout ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Arterial Blood ◽  
Gene Knockout Mouse ◽  
Atrial Natriuretic

Recent findings in atrial natriuretic peptide (ANP) transgenic and gene knockout mouse models uncovered a tonic vasodilatory effect of this hormone that contributes to chronic blood pressure homeostasis. With elevated salt intake, ANP-mediated antagonism of the renin-angiotensin system is essential for blood pressure constancy, suggesting that a deficiency in ANP activity may underlie the etiology of sodium-retaining disorders.

scholarly journals PPARα: Energy Combustion, Hypolipidemia, Inflammation and Cancer

2010 ◽  
Vol 8 (1) ◽  
pp. nrs.08002 ◽  
Author(s):  
Sean R. Pyper ◽  
Navin Viswakarma ◽  
Songtao Yu ◽  
Janardan K. Reddy
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Gene Knockout ◽  
Nuclear Hormone Receptor ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Synthetic Chemicals ◽  
Gene Knockout Mouse ◽  
Lipid Sensor

The peroxisome proliferator-activated receptor α (PPARα, or NR1C1) is a nuclear hormone receptor activated by a structurally diverse array of synthetic chemicals known as peroxisome proliferators. Endogenous activation of PPARα in liver has also been observed in certain gene knockout mouse models of lipid metabolism, implying the existence of enzymes that either generate (synthesize) or degrade endogenous PPARα agonists. For example, substrates involved in fatty acid oxidation can function as PPARα ligands. PPARα serves as a xenobiotic and lipid sensor to regulate energy combustion, hepatic steatosis, lipoprotein synthesis, inflammation and liver cancer. Mainly, PPARα modulates the activities of all three fatty acid oxidation systems, namely mitochondrial and peroxisomal β-oxidation and microsomal co-oxidation, and thus plays a key role in energy expenditure. Sustained activation of PPARα by either exogenous or endogenous agonists leads to the development of hepatocellular carcinoma resulting from sustained oxidative and possibly endoplasmic reticulum stress and liver cell proliferation. PPARα requires transcription coactivator PPAR-binding protein (PBP)/mediator subunit 1(MED1) for its transcriptional activity.

scholarly journals Genetically Altered Mouse Models: the Good, the Bad, and the Ugly

2003 ◽  
Vol 14 (3) ◽  
pp. 154-174 ◽  
Author(s):  
Tamizchelvi Thyagarajan ◽  
Satish Totey ◽  
Mary Jo S. Danton ◽  
Ashok B. Kulkarni
Keyword(s):  
Gene Targeting ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Gene Knockout ◽  
Genetically Engineered ◽  
Murine Models ◽  
Functional Roles ◽  
Targeted Gene Disruption ◽  
Gene Knockout Mouse

Targeted gene disruption in mice is a powerful tool for generating murine models for human development and disease. While the human genome program has helped to generate numerous candidate genes, few genes have been characterized for their precise in vivo functions. Gene targeting has had an enormous impact on our ability to delineate the functional roles of these genes. Many gene knockout mouse models faithfully mimic the phenotypes of the human diseases. Because some models display an unexpected or no phenotype, controversy has arisen about the value of gene-targeting strategies. We argue in favor of gene-targeting strategies, provided they are used with caution, particularly in interpreting phenotypes in craniofacial and oral biology, where many genes have pleiotropic roles. The potential pitfalls are outweighed by the unique opportunities for developing and testing different therapeutic strategies before they are introduced into the clinic. In the future, we believe that genetically engineered animal models will be indispensable for gaining important insights into the molecular mechanisms underlying development, as well as disease pathogenesis, diagnosis, prevention, and treatment.

Tyrosine Hydroxylase Activity and Its mRNA Level in Dopaminergic Neurons of Tenascin Gene Knockout Mouse

1997 ◽  
Vol 231 (2) ◽  
pp. 356-359 ◽  
Author(s):  
Fumihiko Fukamauchi ◽  
Nobuko Mataga ◽  
Yi-Jun Wang ◽  
Shigeo Sato ◽  
Atsushi Yoshiki ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Dopaminergic Neurons ◽  
Knockout Mouse ◽  
Gene Knockout ◽  
Mrna Level ◽  
Hydroxylase Activity ◽  
Tyrosine Hydroxylase Activity ◽  
Gene Knockout Mouse

scholarly journals The Relaxin Gene Knockout Mouse: A Model of Progressive Scleroderma

2005 ◽  
Vol 125 (4) ◽  
pp. 692-699 ◽  
Author(s):  
Chrishan S. Samuel ◽  
Chongxin Zhao ◽  
Qing Yang ◽  
Hong Wang ◽  
Hongsheng Tian ◽  
...  
Keyword(s):  
Knockout Mouse ◽  
Gene Knockout ◽  
Gene Knockout Mouse

Paradoxical behavioral response to apomorphine in tenascin-gene knockout mouse

1997 ◽  
Vol 338 (1) ◽  
pp. 7-10 ◽  
Author(s):  
Fumihiko Fukamauchi ◽  
Yi-Jun Wang ◽  
Nobuko Mataga ◽  
Moriaki Kusakabe
Keyword(s):  
Behavioral Response ◽  
Knockout Mouse ◽  
Gene Knockout ◽  
Gene Knockout Mouse

scholarly journals Neural symptoms in a gene knockout mouse model of Sjögren‐Larsson syndrome are associated with a decrease in 2‐hydroxygalactosylceramide

2018 ◽  
Vol 33 (1) ◽  
pp. 928-941 ◽  
Author(s):  
Tsukasa Kanetake ◽  
Takayuki Sassa ◽  
Koki Nojiri ◽  
Megumi Sawai ◽  
Satoko Hattori ◽  
...  
Keyword(s):  
Mouse Model ◽  
Knockout Mouse ◽  
Gene Knockout ◽  
Knockout Mouse Model ◽  
Gene Knockout Mouse ◽  
Larsson Syndrome

scholarly journals The Gamma Interferon Gene Knockout Mouse: a Highly Sensitive Model for Evaluation of Therapeutic Agents againstCryptosporidium parvum

1998 ◽  
Vol 36 (9) ◽  
pp. 2503-2508 ◽  
Author(s):  
Jeffrey K. Griffiths ◽  
Cynthia Theodos ◽  
Melissa Paris ◽  
Saul Tzipori
Keyword(s):  
Weight Loss ◽  
Clinical Symptoms ◽  
Gene Knockout ◽  
Mammalian Species ◽  
Mucosal Damage ◽  
Gamma Interferon ◽  
Adult Mice ◽  
Malnourished Children ◽  
Gene Knockout Mouse ◽  
Serious Disease

Cryptosporidiosis is a serious disease in malnourished children and in people with malignancies or AIDS. Current rodent models for evaluating drug therapy against cryptosporidiosis have many limitations, including the need for a high inoculum, the absence of symptoms resembling those seen in humans, and the need to maintain exogenous immunosuppression. We have developed a gamma interferon knockout (GKO) mouse model with which to evaluate therapies againstC. parvum and have used paromomycin for evaluation of this model. The GKO model offers considerable improvements over other systems, since it requires no additional immunosuppression and adult mice can be infected with as few as 10 oocysts (compared with 107 for SCID mice). Infected mice develop profound gastrointestinal dysfunction due to extensive infection and severe mucosal damage involving the entire small intestine. Clinical symptoms, which include depression, anorexia, weight loss, and wasting, result in death within 2 to 4 weeks. The time of death depends on the oocyst challenge dose. Paromomycin modulated parasitological and clinical parameters in highly predictable and significant ways, including prevention of death. In addition, examination of the extensively infected gut provided an important insight into the dynamics between a specific drug treatment, its impact on the extent and the site of parasite distribution, and clinical outcome. These uniform symptoms of weight loss, wasting, and death are powerful new parameters which bring this model closer to the actual disease seen in humans and other susceptible mammalian species.

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