Characterizing anisotropic, viscoelastic material properties of the tectorial membranes of wild-type and mutant mice using longitudinally propagating waves

2018 ◽  
Vol 143 (3) ◽  
pp. 1775-1775
Author(s):  
Charlsie Lemons ◽  
Jonathan B. Sellon ◽  
Roberto D. Ortiz ◽  
Elisa Boatti ◽  
Dennis M. Freeman ◽  
...  
Keyword(s):  
Viscoelastic Material ◽  
Material Properties ◽  
Mutant Mice ◽  
Wild Type ◽  
Propagating Waves ◽  
Anisotropic Viscoelastic Material ◽  
Tectorial Membranes

scholarly journals Anisotropic Material Properties of Wild-Type and Tectb−/− Tectorial Membranes

2019 ◽  
Vol 116 (3) ◽  
pp. 573-585 ◽  
Author(s):  
Charlsie Lemons ◽  
Jonathan B. Sellon ◽  
Elisa Boatti ◽  
Daniel Filizzola ◽  
Dennis M. Freeman ◽  
...  
Keyword(s):  
Material Properties ◽  
Anisotropic Material ◽  
Wild Type ◽  
Tectorial Membranes

scholarly journals Alopecia in Harlequin mutant mice is associated with reduced AIF protein levels and expression of retroviral elements

2020 ◽  
Author(s):  
Maik Hintze ◽  
Sebastian Griesing ◽  
Marion Michels ◽  
Birgit Blanck ◽  
Lena Wischhof ◽  
...  
Keyword(s):  
Hair Growth ◽  
Transcriptional Regulators ◽  
Mutant Mice ◽  
Wild Type ◽  
Protein Levels ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Keratinocyte Cell ◽  
Apoptosis Inducing Factor ◽  
Hair Cortex

AbstractWe investigated the contribution of apoptosis-inducing factor (AIF), a key regulator of mitochondrial biogenesis, in supporting hair growth. We report that pelage abnormalities developed during hair follicle (HF) morphogenesis in Harlequin (Hq) mutant mice. Fragility of the hair cortex was associated with decreased expression of genes encoding structural hair proteins, though key transcriptional regulators of HF development were expressed at normal levels. Notably, Aifm1 (R200 del) knockin males and Aifm1(R200 del)/Hq females showed minor hair defects, despite substantially reduced AIF levels. Furthermore, we cloned the integrated ecotropic provirus of the Aifm1Hq allele. We found that its overexpression in wild-type keratinocyte cell lines led to down-regulation of HF-specific Krt84 and Krtap3-3 genes without altering Aifm1 or epidermal Krt5 expression. Together, our findings imply that pelage paucity in Hq mutant mice is mechanistically linked to severe AIF deficiency and is associated with the expression of retroviral elements that might potentially influence the transcriptional regulation of structural hair proteins.

Lingual deficits in BDNF and NT3 mutant mice leading to gustatory and somatosensory disturbances, respectively

Development ◽  
1997 ◽  
Vol 124 (7) ◽  
pp. 1333-1342 ◽  
Author(s):  
C.A. Nosrat ◽  
J. Blomlof ◽  
W.M. ElShamy ◽  
P. Ernfors ◽  
L. Olson
Keyword(s):  
Taste Buds ◽  
Mutant Mice ◽  
Taste Bud ◽  
Physiological Data ◽  
Clinical Implications ◽  
Wild Type ◽  
Severe Reduction ◽  
Sensory Modalities ◽  
Per Se ◽  
Taste Discrimination

A combination of anatomical, histological and physiological data from wild-type and null-mutated mice have established crucial roles for BDNF and NT3 in gustatory and somatosensory innervation of the tongue, and indeed for proper development of the papillary surface of the tongue. BDNF is expressed in taste buds, NT3 in many surrounding epithelial structures. Absence of BDNF in mice leads to severely malformed taste bud-bearing papillae and severe reduction of taste buds, a loss of proper innervation of remaining taste buds and a loss of taste discrimination although not of the suckling reflex per se. In contrast, absence of NT3 leads to a massive loss of somatosensory innervation of lingual structures. These findings demonstrate distinct roles for BDNF and NT3 in the establishment of the complex innervation apparatus of the tongue with non-overlapping roles for the lingual gustatory and somatosensory systems. The distinction between different sensory modalities, being dependent on either BDNF or NT3 may also have clinical implications.

Cardiac dysfunction in mice lacking cytochrome-c oxidase subunit VIaH

2002 ◽  
Vol 282 (2) ◽  
pp. H726-H733 ◽  
Author(s):  
Nina B. Radford ◽  
Bang Wan ◽  
Angela Richman ◽  
Lidia S. Szczepaniak ◽  
Jia-Ling Li ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Cardiac Dysfunction ◽  
Mechanical Performance ◽  
Left Ventricular ◽  
Mutant Mice ◽  
Stroke Work ◽  
Wild Type ◽  
Oxidase Subunit ◽  
End Diastolic Volume

Cytochrome -c oxidase subunit VIaH (COXVIaH) has been implicated in the modulation of COX activity. A gene-targeting strategy was undertaken to generate mice that lacked COXVIaH to determine its role in regulation of oxidative energy production and mechanical performance in cardiac muscle. Total COX activity was decreased in hearts from mutant mice, which appears to be a consequence of altered assembly of the holoenzyme COX. However, total myocardial ATP was not significantly different in wild-type and mutant mice. Myocardial performance was examined using the isolated working heart preparation. As left atrial filling pressure increased, hearts from mutant mice were unable to generate equivalent stroke work compared with hearts from wild-type mice. Direct measurement of left ventricular end-diastolic volume using magnetic resonance imaging revealed that cardiac dysfunction was a consequence of impaired ventricular filling or diastolic dysfunction. These findings suggest that a genetic deficiency of COXVIaH has a measurable impact on myocardial diastolic performance despite the presence of normal cellular ATP levels.

Properties of Mouse Cutaneous Rapidly Adapting Afferents: Relationship to Skin Viscoelasticity

2004 ◽  
Vol 92 (2) ◽  
pp. 1236-1240 ◽  
Author(s):  
P. Grigg ◽  
D. R. Robichaud ◽  
Z. Del Prete
Keyword(s):  
Viscoelastic Material ◽  
Material Properties ◽  
Viscoelastic Properties ◽  
Mechanical Response ◽  
Loss Modulus ◽  
Multiple Logistic Regression Analysis ◽  
Rate Of Change ◽  
Volterra Model ◽  
Lower Sensitivity ◽  
Dynamic Stimuli

When skin is stretched, stimuli experienced by a cutaneous mechanoreceptor neuron are transmitted to the nerve ending through the skin. In these experiments, we tested the hypothesis that the viscoelastic response of the skin influences the dynamic response of cutaneous rapidly adapting (RA) neurons. Cutaneous RA afferent neurons were recorded in 3 species of mice (Tsk, Pallid, and C57BL6) whose skin has different viscoelastic properties. Isolated samples of skin and nerve were stimulated mechanically with a dynamic stretch stimulus, which followed a pseudo Gaussian waveform with a bandwidth of 0–60 Hz. The mechanical response of the skin was measured as were responses of single RA cutaneous mechanoreceptor neurons. For each neuron, the strength of association between spike responses and the dynamic and static components of stimuli were determined with multiple logistic regression analysis. The viscoelastic material properties of each skin sample were determined indirectly, by creating a nonlinear (Wiener–Volterra) model of the stress–strain relationship, and using the model to predict the complex compliance (i.e., the viscoelastic material properties). The dynamic sensitivity of RA mechanoreceptor neurons in mouse hairy skin was weakly related to the viscoelastic properties of the skin. Loss modulus and phase angle were lower (indicating a decreased viscous component of response) in Tsk and Pallid than in C57BL6 mice. However, RA mechanoreceptor neurons in Tsk and Pallid skin did not differ from those in C57 skin with regard to their sensitivity to the rate of change of stress or to the rate of change of incremental strain energy. They did have a decreased sensitivity to the rate of change of tensile strain. Thus the skin samples with lower dynamic mechanical response contained neurons with a somewhat lower sensitivity to dynamic stimuli.

Mice lacking neuronal nicotinic acetylcholine receptor β4-subunit and mice lacking both α5- and β4-subunits are highly resistant to nicotine-induced seizures

2004 ◽  
Vol 17 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Merav Kedmi ◽  
Arthur L. Beaudet ◽  
Avi Orr-Urtreger
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Mutant Mice ◽  
Wild Type ◽  
Nicotinic Acetylcholine ◽  
Nocturnal Frontal Lobe Epilepsy ◽  
Wide Range ◽  
High Doses ◽  
Dose Dependent ◽  
Rate Of Response

Nicotine, the main addictive component of tobacco, evokes a wide range of dose-dependent behaviors in rodents, and when administrated in high doses, it can induce clonic-tonic seizures. Nicotine acts through the nicotinic acetylcholine receptors (nAChRs). Mutations in the human α4- and the β2-nAChR subunit genes cause autosomal dominant nocturnal frontal lobe epilepsy. Using transgenic mice with mutations in nAChR subunits, it was demonstrated previously that the α4-, α5-, and α7-subunits are involved in nicotine-induced seizures. To examine the possibility that the β4-subunit is also involved in this phenotype, we tested mice with homozygous β4-subunit deficiency. The β4 null mice were remarkably resistant to nicotine-induced seizures compared with wild-type and α5 null mice. We also generated mice with double deficiency of both α5- and β4-nAChR subunits and demonstrated that they were more resistant to nicotine’s convulsant effect than either the α5 or the β4 single mutant mice. In addition, the single α5 mutants and the double α5β4-deficient mice exhibited a significantly shorter latency time to seizure than that of the wild-type mice. Our results thus show that β4-containing nAChRs have a crucial role in the pathogenesis of nicotine-induced seizures. Furthermore, by comparing multiple mutant mice with single and double subunit deficiency, we suggest that nicotinic receptors containing either α5- or β4-subunits are involved in nicotine-induced seizures and that receptors containing both subunits are likely to contribute to this phenomena as well. However, the α5-subunit, but not the β4-subunit, regulates the rate of response to high doses of nicotine.

scholarly journals Modulation of HIF-2α PAS-B domain contributes to physiological responses

2018 ◽  
Vol 115 (52) ◽  
pp. 13240-13245 ◽  
Author(s):  
Zhihui Feng ◽  
Xuan Zou ◽  
Yaomin Chen ◽  
Hanzhi Wang ◽  
Yingli Duan ◽  
...  
Keyword(s):  
Body Weight ◽  
Metabolic Regulation ◽  
Body Weight Gain ◽  
Metabolic Stress ◽  
Vital Role ◽  
Mutant Mice ◽  
Single Mutation ◽  
Wild Type ◽  
Adipose Mass

Hypoxia-inducible factors (HIFs) are transcription factors in the basic helix–loop–helix PER-ARNT-SIM (bHLH-PAS) protein family that contain internal hydrophobic cavities within their PAS-A and PAS-B domains. Among HIFs, the HIF-2α PAS-B domain contains a relatively large cavity exploited for the development of specific artificial ligands such as PT2399. Administration of PT2399 could suppress HIF-2α target gene expression without affecting HIF-1 activity in mice under hypoxia conditions. A single mutation (S305M) within the HIF-2α PAS-B domain suppressed HIF-2α activity while conferring resistance to PT2399 in vivo, indicating the vital role of PAS-B domain in HIF-2α hypoxia response. In contrast, the mutant mice did not phenocopy PT2399 intervention in wild-type mice under metabolic stress. Under a high-fat diet (HFD), the mutant mice exert enhanced adipogenesis and obtain larger adipose mass and body weight gain compared to wild type. However, administration of PT2399 along with HFD feeding sufficiently suppressed HFD-induced body weight and adipose mass increase through suppression of adipogenesis and lipogenesis. The accompanying decreased lipid accumulation in the liver and improved glucose tolerance in wild-type mice were not observed in the mutant mice indicating negative regulation of HIF-2α on obesity and a complex role for the PAS-B domain in metabolic regulation. Notably, short-term administration of PT2399 to obese mice decreased adipose mass and improved metabolic condition. These results indicate a regulatory role for HIF-2α in obesity progression and suggest a therapeutic opportunity for PT2399 in obesity and associated metabolic disorders.

scholarly journals An Autism-Associated Neuroligin-3 Mutation Affects Developmental Synapse Elimination in the Cerebellum

2021 ◽  
Vol 15 ◽  
Author(s):  
Esther Suk King Lai ◽  
Hisako Nakayama ◽  
Taisuke Miyazaki ◽  
Takanobu Nakazawa ◽  
Katsuhiko Tabuchi ◽  
...  
Keyword(s):  
Cell Adhesion Molecule ◽  
Synapse Formation ◽  
Single Point ◽  
Autism Spectrum ◽  
Mutant Mice ◽  
Single Point Mutation ◽  
Synapse Elimination ◽  
Wild Type ◽  
Post Mortem Brain ◽  
And Function

Neuroligin is a postsynaptic cell-adhesion molecule that is involved in synapse formation and maturation by interacting with presynaptic neurexin. Mutations in neuroligin genes, including the arginine to cystein substitution at the 451st amino acid residue (R451C) of neuroligin-3 (NLGN3), have been identified in patients with autism spectrum disorder (ASD). Functional magnetic resonance imaging and examination of post-mortem brain in ASD patients implicate alteration of cerebellar morphology and Purkinje cell (PC) loss. In the present study, we examined possible association between the R451C mutation in NLGN3 and synaptic development and function in the mouse cerebellum. In NLGN3-R451C mutant mice, the expression of NLGN3 protein in the cerebellum was reduced to about 10% of the level of wild-type mice. Elimination of redundant climbing fiber (CF) to PC synapses was impaired from postnatal day 10–15 (P10–15) in NLGN3-R451C mutant mice, but majority of PCs became mono-innervated as in wild-type mice after P16. In NLGN3-R451C mutant mice, selective strengthening of a single CF relative to the other CFs in each PC was impaired from P16, which persisted into juvenile stage. Furthermore, the inhibition to excitation (I/E) balance of synaptic inputs to PCs was elevated, and calcium transients in the soma induced by strong and weak CF inputs were reduced in NLGN3-R451C mutant mice. These results suggest that a single point mutation in NLGN3 significantly influences the synapse development and refinement in cerebellar circuitry, which might be related to the pathogenesis of ASD.

Sign in / Sign up

Export Citation Format

Share Document