scholarly journals CD-1 Outbred Mice Produce Less Variable Ultrasonic Vocalizations Than FVB Inbred Mice, While Displaying a Similar Developmental Trajectory

2021 ◽  
Vol 12 ◽  
Author(s):  
Matthew S. Binder ◽  
Hannah D. Shi ◽  
Angelique Bordey
Keyword(s):  
Maternal Care ◽  
Inbred Mice ◽  
Mean Amplitude ◽  
Developmental Trajectory ◽  
Ultrasonic Vocalizations ◽  
Neurological Deficits ◽  
Male And Female ◽  
Outbred Mice ◽  
Cd1 Mice ◽  
Relative Variability

The production of ultrasonic vocalizations (USVs) in neonatal mice is a critical means of communication that is used to elicit maternal care. Alterations in neonatal USV production is also an indicator of neurological deficits. However, USVs have been predominately assessed in inbred animals and are significantly understudied in outbred mice, even though outbred animals better represent the genetic diversity of humans and are used in several neurological disorder models. To determine the reproducibility of USVs across models, we compared male and female CD-1 (outbred) and FVB (inbred) mice on postnatal days (PD) 4, 8, 12, 16, and 20. We found that CD-1 and FVB mice displayed a similar developmental trajectory of USVs. However, CD1 mice emitted more USVs on PD 12 than FVB mice. In addition, FVB mice emitted a longer duration of calls on PD 4 and 8 and a higher overall maximum and minimum frequency of USVs than CD-1 mice. No differences in mean amplitude were found between groups. We also detected numerous significant differences between outbred and inbred mice when comparing each group's call composition. We next assessed the relative variability of mouse vocalizations between groups, finding that outbred mice were less variable than inbred mice. For the spectral and temporal characteristics of the USVs, variability was similar between groups. Altogether, we found that CD-1 outbred mice display a similar, if not lower, degree of variability than FVB inbred mice when assessing neonatal USVs.

The Ontogeny of Ultrasonic Vocalization in Microtus Montanus

Behaviour ◽  
1977 ◽  
Vol 60 (1-2) ◽  
pp. 115-121 ◽  
Author(s):  
V.J. De Ghett
Keyword(s):  
Short Duration ◽  
Maternal Care ◽  
Ultrasonic Vocalization ◽  
Ultrasonic Vocalizations ◽  
Developmental Changes ◽  
Maternal Behaviour ◽  
Postnatal Ontogeny ◽  
Microtus Montanus ◽  
Early Peak ◽  
The Mean

AbstractDevelopmental changes in parameters of ultrasound production were investigated in M. montanus young. The rate of ultrasonic vocalization reached a peak on Day 2 of postnatal ontogeny and declined to zero on Day 15. A similar developmental pattern has been found in several other rodent species. However, the comparatively early peak rate is indicative of a degree of ontogenic precociousness. Other developmental changes, both behavioural and morphological, tend to confirm that M. montanus young are relatively precocious. The duration of ultrasonic vocalizations did not show a significant change across early development. The mean duration for each vocalization sampled was 22.92 msec. The distribution of these vocalizations showed that a considerable number of vocalizations were of very short duration (<30 msec). The developmental changes in the percentage of young emitting ultrasounds began to decline following Day 8 and reached zero percent on Day 15. This decline in the percentage of young vocalizing corresponded to changes in maternal behaviour. Both the rate of ultrasonic vocalization and the percentage of young vocalizing were significantly correlated with the age of the young. Being correlated with age, these parameters of ultrasound production have the possibility of having great communicative value for the purposes of maternal care.

scholarly journals Comparison of the Susceptibilities of C57BL/6 and A/J Mouse Strains to Streptococcus suis Serotype 2 Infection

2008 ◽  
Vol 76 (9) ◽  
pp. 3901-3910 ◽  
Author(s):  
María de la Cruz Domínguez-Punaro ◽  
Mariela Segura ◽  
Danuta Radzioch ◽  
Serge Rivest ◽  
Marcelo Gottschalk
Keyword(s):  
Septic Shock ◽  
Inbred Mice ◽  
Late Phase ◽  
Streptococcus Suis ◽  
Mouse Strains ◽  
Necrosis Factor Alpha ◽  
Central Nervous System Damage ◽  
Proinflammatory Mediators ◽  
Outbred Mice

ABSTRACT Streptococcus suis is an important swine and human pathogen. Assessment of susceptibility to S. suis using animal models has been limited to monitoring mortality rates. We recently developed a hematogenous model of S. suis infection in adult CD1 outbred mice to study the in vivo development of an early septic shock-like syndrome that leads to death and a late phase that clearly induces central nervous system damage, including meningitis. In the present study, we compared the severities of septic shock-like syndrome caused by S. suis between adult C57BL/6J (B6) and A/J inbred mice. Clinical parameters, proinflammatory mediators, and bacterial clearance were measured to dissect potential immune factors associated with genetic susceptibility to S. suis infection. Results showed that A/J mice were significantly more susceptible than B6 mice to S. suis infection, especially during the acute septic phase of infection (100% of A/J and 16% of B6 mice died before 24 h postinfection). The greater susceptibility of A/J mice was associated with an exaggerated inflammatory response, as indicated by their higher production of tumor necrosis factor alpha, interleukin-12p40/p70 (IL-12p40/p70), gamma interferon, and IL-1β, but not with different bacterial loads in the blood. In addition, IL-10 was shown to be responsible, at least in part, for the higher survival in B6 mice. Our findings demonstrate that A/J mice are very susceptible to S. suis infection and provide evidence that the balance between pro- and anti-inflammatory mediators is crucial for host survival during the septic phase.

scholarly journals Long-term decreased cannabinoid type-1 receptor activity restores specific neurological phenotypes in the Ts65Dn mouse model of Down syndrome

2021 ◽  
Author(s):  
Anna Vazquez-Oliver ◽  
Silvia Perez-Garcia ◽  
Nieves Pizarro ◽  
Laura Molina-Porcel ◽  
Rafael de la Torre ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Side Effects ◽  
Mouse Model ◽  
Neurological Deficits ◽  
Wild Type ◽  
Male And Female ◽  
Cannabinoid Type 1 Receptor ◽  
Cognitive Improvement

Intellectual disability is the most prevalent and limiting hallmark of Down syndrome (DS), without any pharmacological treatment available. Neurodegeneration and neuroinflammation are relevant neurological features of DS reaching to early development of Alzheimer s disease. Preclinical evidence suggests that the endocannabinoid system, an important neuromodulator on cognition and neuroinflammation, could act as beneficial target in DS. Indeed, cannabinoid type-1 receptor (CB1R) activity was enhanced in the hippocampus of young-adult trisomic Ts65Dn mice, a well-characterized surrogate model of DS. In previous studies, inhibition of CB1R, was able to restore key neurological deficits in this mouse model. To determine the possible clinical relevance of this target, it is mandatory to evaluate the long-term consequences of attenuated CB1R activity and to minimize the possible side-effects associated to this mechanism. We found that CB1R expression was significantly enhanced in the hippocampus brains of aged DS subjects. Similarly, middle-aged trisomic mice showed enhanced CB1R expression. Long-term oral administration of a low dose of the CB1R specific antagonist rimonabant was administered to male and female Ts65Dn trisomic and wild-type mice from the time of weaning to 10 months, an age when signs of neurodegeneration have been described in the model. CB1R inhibition resulted in significant cognitive improvement in novel object-recognition memory in trisomic male and female mice, reaching a similar performance to that of wild-type littermates. Interestingly, this long-term rimonabant treatment modify locomotor activity, anxiety-like behavior, body weight or survival rates. Brain analysis at 10 months of age revealed noradrenergic and cholinergic neurodegeneration signs in trisomic mice that were not modified by the treatment, although the alterations in hippocampal microglia morphology shown by vehicle-treated trisomic mice was normalized in trisomic mice exposed to rimonabant. Altogether, our results demonstrate a sustained pro-cognitive effect of CB1R inhibition at doses that do not produce major side effects that could be associated to an anti-inflammatory action, suggesting a potential interest in this target of to preserve cognitive functionality in DS.

Abstract WP291: Diabetes Impairs Long-term Functional Recovery in an Embolic Stroke Model in Sex Independent Manner

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Weiguo Li ◽  
Sherif Hafez ◽  
John Paul Valenzuela ◽  
Rebecca Ward ◽  
Guangkuo Dong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Hemorrhagic Transformation ◽  
Cognitive Outcome ◽  
Embolic Stroke ◽  
Neurological Deficits ◽  
Independent Manner ◽  
Male And Female ◽  
The Impact

Ischemic stroke is a leading cause of death and disability. Diabetes not only increases the risk of stroke, it also worsens the outcomes, increases the risk of hemorrhagic transformation (HT) and impairs recovery after stroke. It is well established that young females are more protected and show better outcomes than males after stroke. However, the impact of diabetes on long term recovery after stroke in both sexes was not clear. Accordingly, this study tested the hypothesis that diabetes impairs long term functional recovery after ischemic stroke in a sex independent manner. Methods: Diabetes was induced in male and female Wistar rats using high fat diet and low dose streptozotocin (30 mg/Kg). After 8 weeks of diabetes, animals were subjected to embolic stroke. Male and female Wistar normoglycemic age matched rats were used as controls. Motor (composite score: 14 best outcome and adhesive removal-ART) and cognitive (novel object recognition, NOR) deficits were assessed at day1, 3, 7 and 14. Results: Female control animals had better outcomes compared to the males. Mortality was higher in diabetic animals, especially in males. The neurological deficits were greater in diabetic animals with no difference between males and females. Conclusion: Diabetes impaired functional and cognitive outcome and recovery after ischemic stroke in a sex independent manner.

scholarly journals A Comparison of Ketamine or Etomidate Combined with Xylazine for Intraperitoneal Anesthesia in Four Mouse Strains

2020 ◽  
Vol 59 (5) ◽  
pp. 519-530
Author(s):  
Crystal H Gergye ◽  
Yixuan Zhao ◽  
Reneé H Moore ◽  
Vanessa K Lee
Keyword(s):  
Blood Pressure ◽  
Veterinary Medicine ◽  
Systolic Blood Pressure ◽  
Rectal Temperature ◽  
High Rate ◽  
Mouse Strains ◽  
Invasive Procedures ◽  
Male And Female ◽  
Cd1 Mice ◽  
Strain Dependent

Intraperitoneal (IP) injection is a common route of anesthetic administration in mice. Ketamine-xylazine (KX) anesthesia is one of the most widely used IP protocols, but has limitations. Etomidate is an alternative to ketamine that has been used in both human and veterinary medicine yet has not been widely studied in mice. The purpose of this study was to evaluate etomidate-xylazine (EX) anesthesia as an alternative to KX. We hypothesized that EX would be as safe and effective as KX, with both sex- and strain-dependent differences. Male and female Crl:CD1(ICR), C57BL/6NCrl, BALB/cJ and NU/J mice were given a single IP dose of ketamine 100 mg/kg and xylazine 10 mg/kg or etomidate 20 mg/kg and xylazine 10 mg/kg. Sedation times were similar between KX and EX, with CD1 mice exhibiting shorter sedation times. Surgical anesthesia was achieved in 44% of EX mice, compared with 4% of KX mice. C57BL/6NCrl mice were significantly more likely to achieve surgical anesthesia when given EX (94%) or KX (18%) than were other strains. In all strains except C57BL/6NCrl mice, females were more likely to reach surgical anesthesia than males. Several mice experienced an adverse hyperexcitement response during induction, with BALB/cJ (79%) and NU/J (87%) mice given EX significantly more likely than other strains to experience hyperexcitement. EX and KX protocols had no overall differences in lowest respiration rate, lowest systolic blood pressure, lowest rectal temperature, or levels of acidosis, although the lowest heart rates were significantly higher with EX, indicating that EX and KX have similar safety profiles. Thus, EX and KX administration were associated with several significant physiologic differences when comparing sexes or individual strains. Our results indicate that EX is an equally effective sedative and a more effective surgical anesthetic than KX; however, EX is only recommended for invasive procedures in C57BL/6 mice due to the high rate of hyper-excitement and inconsistent surgical depth seen in other strains. Further study is needed to optimize EX for use in multiple mouse strains.

Mapping of Genes That Control the Antibody Response to Human FVIII in Mice.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1888-1888
Author(s):  
Jay Nelson Lozier ◽  
Pei Zhang
Keyword(s):  
Antibody Response ◽  
Mouse Chromosome ◽  
Recombinant Inbred ◽  
Inbred Mice ◽  
Antibody Responses ◽  
Polymorphic Markers ◽  
Suggestive Linkage ◽  
Lod Score ◽  
Male And Female ◽  
Recombinant Inbred Mice

Abstract In our previous studies of genetic factors that influence the immune response (particularly inhibitor antibodies) to therapeutic coagulation factors we have shown that H2 and cytokine genes control the antibody response to human FIX protein in mice (Lozier et al., Blood105:1029–1035, 2005). We have extended our investigation to the murine resonse to human FVIII. Based on the observation that FVIII K/O mice in Balb/cByJ and C57BL/6ByJ backgrounds have significantly different antibody responses to human FVIII after gene transfer (Brown et al., J Thromb Haemost2:111–8, 2004) we studied the antibody response to human FVIII in these mice and 13 CXB recombinant inbred mouse lines derived from these parental strains. Balb/cByJ mice were significantly higher responders to human FVIII than C57BL/6ByJ mice after a single injection with an adenovirus vector (AVPGKf8mg) expressing human FVIII (P < 0.001) or serial intravenous injections of human FVIII protein sans adjuvant (P < 0.01). For both strains the difference between male and female antibody responses following adenovirus or FVIII protein injections were not significantly different. Phage display mapping with 7-mer looped and 12-mer linear libraries showed reactivity against epitopes in the A1, A2, B, and C1 domains of human FVIII as well as the acidic region between the A1/A2 domains, after administration of FVIII protein. Analysis of antibody titers to human FVIII in male CXB recombinant inbred mice after weight-adjusted doses of AVPGKF8mg vector revealed suggestive linkage-relatedness scores for a series of polymorphic markers on mouse chromosome 8 that are 40–45 centimorgans from the centromere. These include D8mit 240 (LOD score 3.1), D8mit45 (LOD score 3.1), and D8mit84 (LOD score 3.0). Each marker had an equal additive effect to the antibody response. In female CXB recombinant inbred mice different markers were associated with the antibody response to FVIII than in males. For female CXB recombinant inbred mice there were suggestive linkage relatedness scores for polymorphic markers on mouse chromosome 17 (D17mit16, LOD score 3.0) and mouse chromosome 5 (D5mit31, LOD score 2.4). Both markers had equal additive effects on the antibody response to human FVIII. D17mit16 is adjacent to the mouse H2 gene complex, an obvious candidate for genetic control of the immune response. D5mit31 is a polymorphic marker associated with the zinc alpha-2-glycoprotein I (AZGP) gene on mouse chromosome 5. AZGP is a 307 amino acid plasma glycoprotein whose physiologic function involves regulation of lipolysis. It has homology to class I protein in its amino terminus and to the immunoglobulin constant domain at its carboxy terminus. AZGP binds lipids and zinc, which raises the possibility that it may relate to FVIII protein by mutual interaction with lipids and/or transition metals (e.g., copper/zinc). Our FVIII antibody linkage results differs from our previous work with FIX in that the linkage scores are not as high for the anti-FVIII response as for the anti-FIX response. Further, in this study there are different polymorphic markers associated with the antibody response in male and female mice. We continue to investigate genes in mice that control the antibody response to factors VIII and IX in order to identify and predict candidate genes that should be investigated in higher animal models of hemophilia (e.g., hemophilia A and B dogs) as well as in humans with hemophilia.

scholarly journals Corrigendum: Wired for motherhood: induction of maternal care but not maternal aggression in virgin female CD1 mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Ana Martín-Sánchez ◽  
Guillermo Valera-Marín ◽  
Adoración Hernández-Martínez ◽  
Enrique Lanuza ◽  
Fernando Martínez-García ◽  
...  
Keyword(s):  
Maternal Care ◽  
Virgin Female ◽  
Maternal Aggression ◽  
Cd1 Mice

scholarly journals Trajectories of Mother-Infant Communication: An Experiential Measure of the Impacts of Early Life Adversity

2021 ◽  
Vol 15 ◽  
Author(s):  
Lauren Granata ◽  
Alissa Valentine ◽  
Jason L. Hirsch ◽  
Jennifer Honeycutt ◽  
Heather Brenhouse
Keyword(s):  
Maternal Care ◽  
Early Life ◽  
Maternal Separation ◽  
Developmental Trajectories ◽  
Later Life ◽  
Developmental Trajectory ◽  
Acoustic Properties ◽  
Emission Rates ◽  
Acoustic Parameters ◽  
Early Life Adversity

Caretaking stability in the early life environment supports neurobehavioral development, while instability and neglect constitute adverse environments that can alter maturational processes. Research in humans suggests that different types of early life adversity (ELA) can have differential effects on caretaker relationships and later cognitive and social development; however, identifying mechanistic underpinnings will require animal models with translational validity. Two common rodent models, maternal separation (MS) and limited bedding (LB), influence the mother-infant relationship during a critical window of development. We hypothesized that these paradigms may affect the development of communication strategies on the part of the pup. Ultrasonic vocalizations (USVs) are a care-eliciting mechanism and ethologically relevant response to stressors in the rat pup. USV emission rates and acoustic parameters change throughout early development, presenting the opportunity to define developmental milestones in USVs that would reflect neurobehavioral aberrations if disrupted. This study investigated the effects of MS or LB on the dam-pup relationship by quantifying pup USVs, maternal behavior, and the relationship between the two. First, we used a generalized additive model approach to establish typical developmental trajectories of USV acoustic properties and determine windows of change in MS or LB rearing. Additionally, we quantified maternal behaviors and the predictability of maternal care sequences using an entropy rate calculation. MS and LB each shifted the developmental trajectories of USV acoustic parameters and call types in a sex-specific manner. MS more often impacted male USVs, while LB impacted female USVs. MS dams spent more time passive nursing, and LB dams spent more time on the nest. The predictability of maternal care was associated with the rate of USV emissions exclusively in females. Taken together, findings demonstrate sex- and model-specific effects of rearing environments on a novel developmental trajectory involving the mother-infant relationship, facilitating the translation of animal ELA paradigms to assess later-life consequences.

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