scholarly journals Sex-Related Motor Deficits in the Tau-P301L Mouse Model

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1160
Author(s):  
Luana Cristina Camargo ◽  
Dominik Honold ◽  
Robert Bauer ◽  
N. Jon Shah ◽  
Karl-Josef Langen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mouse Models ◽  
Behavioral Changes ◽  
Motor Deficits ◽  
The Novel ◽  
Behavioral Alterations ◽  
Object Recognition Test ◽  
Histological Changes ◽  
Female Mice

The contribution of mouse models for basic and translational research at different levels is important to understand neurodegenerative diseases, including tauopathies, by studying the alterations in the corresponding mouse models in detail. Moreover, several studies demonstrated that pathological as well as behavioral changes are influenced by the sex. For this purpose, we performed an in-depth characterization of the behavioral alterations in the transgenic Tau-P301L mouse model. Sex-matched wild type and homozygous Tau-P301L mice were tested in a battery of behavioral tests at different ages. Tau-P301L male mice showed olfactory and motor deficits as well as increased Tau pathology, which was not observed in Tau-P301L female mice. Both Tau-P301L male and female mice had phenotypic alterations in the SHIRPA test battery and cognitive deficits in the novel object recognition test. This study demonstrated that Tau-P301L mice have phenotypic alterations, which are in line with the histological changes and with a sex-dependent performance in those tests. Summarized, the Tau-P301L mouse model shows phenotypic alterations due to the presence of neurofibrillary tangles in the brain.

scholarly journals Delayed Dopamine Dysfunction and Motor Deficits in Female Parkinson Model Mice

2019 ◽  
Vol 20 (24) ◽  
pp. 6251 ◽  
Author(s):  
Yuan-Hao Chen ◽  
Vicki Wang ◽  
Eagle Yi-Kung Huang ◽  
Yu-Ching Chou ◽  
Tung-Tai Kuo ◽  
...  
Keyword(s):  
Gender Differences ◽  
Mouse Model ◽  
Motor Behavior ◽  
Epidemiological Data ◽  
Behavioral Changes ◽  
Motor Deficits ◽  
Female Mice ◽  
Progressive Loss ◽  
Symptom Progression ◽  
Da Release

This study analyzed gender differences in the progressive dopamine (DA) deficiency phenotype in the MitoPark (MP) mouse model of Parkinson’s disease (PD) with progressive loss of DA release and reuptake in midbrain DA pathways. We found that the progressive loss of these DA presynaptic parameters begins significantly earlier in male than female MP mice. This was correlated with behavioral gender differences of both forced and spontaneous motor behavior. The degeneration of the nigrostriatal DA system in MP mice is earlier and more marked than that of the mesolimbic DA system, with male MP mice again being more strongly affected than female MP mice. After ovariectomy, DA presynaptic and behavioral changes in female mice become very similar to those of male animals. Our results suggest that estrogen, either directly or indirectly, is neuroprotective in the midbrain DA system. Our results are compatible with epidemiological data on incidence and symptom progression in PD, showing that men are more strongly affected than women at early ages.

Aberrant palmitoylation in Huntington disease

2015 ◽  
Vol 43 (2) ◽  
pp. 205-210 ◽  
Author(s):  
Shaun S. Sanders ◽  
Michael R. Hayden
Keyword(s):  
Mouse Model ◽  
Mouse Models ◽  
Huntington Disease ◽  
Motor Deficits ◽  
Adult Onset ◽  
Interacting Protein ◽  
Genetic Ablation ◽  
Neuronal Toxicity ◽  
Cag Expansion ◽  
Huntingtin Interacting Protein

Huntington disease (HD) is an adult-onset neurodegenerative disease caused by a CAG expansion in the HTT gene. HD is characterized by striatal atrophy and is associated with motor, cognitive and psychiatric deficits. In the presence of the HD mutation, the interactions between huntingtin (HTT) and huntingtin interacting protein 14 (HIP14 or DHHC17) and HIP14-like (DHHC13, a HIP14 orthologue), palmitoyl acyltransferases for HTT, are disturbed, resulting in reduced palmitoylation of HTT. Genetic ablation of either Hip14 or Hip14l recapitulates many features of HD, including striatal atrophy and motor deficits. However, there are no changes in palmitoylation of HTT in either mouse model and, subsequently, the similarities between the phenotypes of these two mouse models and the HD mouse model are believed to result from underpalmitoylation of other HIP14 and HIP14L substrates. HTT acts as a modulator of HIP14 activity such that in the presence of the HD mutation, HIP14 is less active. Consequently, HIP14 substrates are less palmitoylated, leading to neuronal toxicity. This suggests that altered HIP14–HTT and HIP14L–HTT interactions in the presence of the HD mutation reduces palmitoylation and promotes mislocalization of HTT and other HIP14/HIP14L substrates. Ultimately, HD may be, in part, a disease of altered palmitoylation.

scholarly journals Developmental and behavioral phenotypes in a new mouse model of DDX3X syndrome

2021 ◽  
Author(s):  
Andrea Boitnott ◽  
Dévina C Ung ◽  
Marta Garcia-Forn ◽  
Kristi Niblo ◽  
Danielle Mendonca ◽  
...  
Keyword(s):  
Mouse Model ◽  
Behavioral Problems ◽  
Behavioral Changes ◽  
Face Validity ◽  
Motor Deficits ◽  
Projection Neurons ◽  
Loss Of Function ◽  
Cortical Projection ◽  
Glutamatergic Neurons ◽  
Brain Malformations

ABSTRACTBackgroundMutations in the X-linked gene DDX3X account for ~2% of intellectual disability in females, often co-morbid with behavioral problems, motor deficits, and brain malformations. DDX3X encodes an RNA helicase with emerging functions in corticogenesis and synaptogenesis.MethodsWe generated a Ddx3x haploinsufficient mouse (Ddx3x+/−) with construct validity for DDX3X loss-of-function mutations. We used standardized batteries to assess developmental milestones and adult behaviors, as well as magnetic resonance imaging and immunostaining of cortical projection neurons to capture early postnatal changes in brain development.ResultsDdx3x+/− mice show physical, sensory, and motor delays that evolve into behavioral anomalies in adulthood, including hyperactivity, anxiety-like behaviors, cognitive impairments, and motor deficits. Motor function further declines with age. These behavioral changes are associated with a reduction in brain volume, with some regions (e.g., cortex and amygdala) disproportionally affected. Cortical thinning is accompanied by defective cortical lamination, indicating that Ddx3x regulates the balance of glutamatergic neurons in the developing cortex.ConclusionsThese data shed new light on the developmental mechanisms driving DDX3X syndrome and support face validity of this novel pre-clinical mouse model.

scholarly journals Characterization of early-onset motor deficits in the Pink1−/− mouse model of Parkinson disease

2018 ◽  
Vol 1680 ◽  
pp. 1-12 ◽  
Author(s):  
Cynthia A. Kelm-Nelson ◽  
Alexander F.L. Brauer ◽  
Kelsey J. Barth ◽  
Jacob M. Lake ◽  
Mackenzie L.K. Sinnen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Parkinson Disease ◽  
Early Onset ◽  
Motor Deficits

scholarly journals Characterization of Neurophysiological and Behavioral Changes, MRI Brain Volumetry and 1H MRS in zQ175 Knock-In Mouse Model of Huntington's Disease

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e50717 ◽  
Author(s):  
Taneli Heikkinen ◽  
Kimmo Lehtimäki ◽  
Nina Vartiainen ◽  
Jukka Puoliväli ◽  
Susan J. Hendricks ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Behavioral Changes ◽  
1H Mrs ◽  
Mri Brain ◽  
Brain Volumetry

scholarly journals Generation of a New Frizzled 2 Flox Mouse Model to Clarify Its Role in Development

2021 ◽  
Author(s):  
Megan N. Michalski ◽  
Cassandra R. Diegel ◽  
Zhendong A. Zhong ◽  
Kelly Suino-Powell ◽  
Levi Blazer ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Tissue Specific ◽  
Knockout Mouse Model ◽  
Full Characterization ◽  
Specific Effects ◽  
Embryonic Lethal ◽  
Early Lethality

AbstractIt is currently accepted that Wnt receptors, Frizzleds (Fzd), have high functional redundancy, making individual receptors challenging to target therapeutically. Specifically, Fzd2 is believed to be functionally redundant with Fzd1 and Fzd7, findings which were based largely on previously published global knockout mouse studies. Conversely, a Fzd2 global knockout mouse model developed by the International Mouse Phenotype Consortium (IMPC) is early embryonic lethal, suggesting Fzd2 is critical for early embryonic development. If global deletion of Fzd2 leads to early lethality, floxed models are necessary to identify tissue-specific phenotypes. We found that a previously published Fzd2 flox model does not fully delete Fzd2 function. To reconcile the contradictory findings in Fzd2 mouse models and allow for tissue-specific studies of Fzd2, we have generated a new flox model using a modified two-cell homologous recombination CRISPR approach. We demonstrated successful simultaneous insertion of two loxP sites fully surrounding the Fzd2 gene and confirmed cre-mediated recombination deletes the sequence between the loxP sites leading to a Fzd2 null allele. Preliminary studies suggest global knockouts are early embryonic lethal and full characterization of the tissue-specific effects of Fzd2 deletion is currently underway. This work suggests Fzd2 uniquely regulates development and emphasizes the importance of thorough validation of newly generated mouse models.

scholarly journals Metabolic, Phenotypic, and Neuropathological Characterization of the Tg4-42 Mouse Model for Alzheimer’s Disease

2021 ◽  
Vol 80 (3) ◽  
pp. 1151-1168
Author(s):  
Barbara Hinteregger ◽  
Tina Loeffler ◽  
Stefanie Flunkert ◽  
Joerg Neddens ◽  
Thomas A. Bayer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Mouse Models ◽  
Neuronal Degeneration ◽  
Integrated Approach ◽  
In Vivo Model ◽  
Preclinical Research

Background: Preclinical Alzheimer’s disease (AD) research strongly depends on transgenic mouse models that display major symptoms of the disease. Although several AD mouse models have been developed representing relevant pathologies, only a fraction of available mouse models, like the Tg4-42 mouse model, display hippocampal atrophy caused by the death of neurons as the key feature of AD. The Tg4-42 mouse model is therefore very valuable for use in preclinical research. Furthermore, metabolic biomarkers which have the potential to detect biochemical changes, are crucial to gain deeper insights into the pathways, the underlying pathological mechanisms and disease progression. Objective: We thus performed an in-depth characterization of Tg4-42 mice by using an integrated approach to analyze alterations of complex biological networks in this AD in vivo model. Methods: Therefore, untargeted NMR-based metabolomic phenotyping was combined with behavioral tests and immunohistological and biochemical analyses. Results: Our in vivo experiments demonstrate a loss of body weight increase in homozygous Tg4-42 mice over time as well as severe impaired learning behavior and memory deficits in the Morris water maze behavioral test. Furthermore, we found significantly altered metabolites in two different brain regions and metabolic changes of the glutamate/4-aminobutyrate-glutamine axis. Based on these results, downstream effects were analyzed showing increased Aβ42 levels, increased neuroinflammation as indicated by increased astro- and microgliosis as well as neuronal degeneration and neuronal loss in homozygous Tg4-42 mice. Conclusion: Our study provides a comprehensive characterization of the Tg4-42 mouse model which could lead to a deeper understanding of pathological features of AD. Additionally this study reveals changes in metabolic biomarker which set the base for future preclinical studies or drug development.

789: Characterization of the novel Npas2 cKO mouse model indicates role in regulating metabolic homeostasis

2015 ◽  
Vol 212 (1) ◽  
pp. S382
Author(s):  
Derek O'Neil ◽  
Danielle Goodspeed ◽  
Laura Krannich ◽  
Kjersti Aagaard
Keyword(s):  
Mouse Model ◽  
The Novel ◽  
Metabolic Homeostasis

scholarly journals Restoring memory by optogenetic synchronization of hippocampal oscillations in an Alzheimer’s disease mouse model

2018 ◽  
Author(s):  
Eleonora Ambrad Giovannetti ◽  
Stefanie Poll ◽  
Daniel Justus ◽  
Hiroshi Kaneko ◽  
Falko Fuhrmann ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Field Potential ◽  
Temporal Organization ◽  
Theta Oscillations ◽  
The Novel ◽  
Object Recognition Test ◽  
Reduced Frequency ◽  
Local Field Potential Lfp

Disrupted neural oscillations are a feature of Alzheimer’s disease (AD). We observed reduced frequency of theta oscillations in the hippocampal local field potential (LFP) in a mouse model of beta-amyloidosis. By restoring the temporal organization of theta oscillations using LFP-guided closed-loop optogenetic stimulation of parvalbumin-positive interneurons, we could rescue memory deficits of APP/PS1 mice in the novel object recognition test.

scholarly journals Gender Related Changes in Gene Expression Induced by Valproic Acid in A Mouse Model of Autism and the Correction by S-adenosyl Methionine. Does It Explain the Gender Differences in Autistic Like Behavior?

2019 ◽  
Vol 20 (21) ◽  
pp. 5278 ◽  
Author(s):  
Liza Weinstein-Fudim ◽  
Zivanit Ergaz ◽  
Gadi Turgeman ◽  
Joseph Yanai ◽  
Moshe Szyf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gender Differences ◽  
Valproic Acid ◽  
Prefrontal Cortex ◽  
Mouse Model ◽  
Behavioral Changes ◽  
Male And Female ◽  
Female Mice ◽  
Adenosyl Methionine ◽  
Males And Females

In previous studies we produced autism like behavioral changes in mice by Valproic acid (VPA) with significant differences between genders. S-adenosine methionine (SAM) prevented the autism like behavior in both genders. The expression of 770 genes of pathways involved in neurophysiology and neuropathology was studied in the prefrontal cortex of 60 days old male and female mice using the NanoString nCounter. In females, VPA induced statistically significant changes in the expression of 146 genes; 71 genes were upregulated and 75 downregulated. In males, VPA changed the expression of only 19 genes, 16 were upregulated and 3 downregulated. Eight genes were similarly changed in both genders. When considering only the genes that were changed by at least 50%, VPA changed the expression of 15 genes in females and 3 in males. Only Nts was similarly downregulated in both genders. SAM normalized the expression of most changed genes in both genders. We presume that genes that are involved in autism like behavior in our model were similarly changed in both genders and corrected by SAM. The behavioral and other differences between genders may be related to genes that were differently affected by VPA in males and females and/or differently affected by SAM.

Sign in / Sign up

Export Citation Format

Share Document