63 research outputs found

    A Role for Strain Differences in Waveforms of Ultrasonic Vocalizations during Male–Female Interaction

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    Male mice emit ultrasonic vocalizations (USVs) towards females during male–female interaction. It has been reported that USVs of adult male mice have the capability of attracting females. Although the waveform pattern of USVs is affected by genetic background, differences among strains with respect to USV and the effects of these differences on courtship behavior have not been analyzed fully. We analyzed USV patterns, as well as actual social behavior during USV recording, in 13 inbred mouse strains, which included laboratory and wild-derived strains. Significant effects of strain were observed for the frequency of USV emission, duration, and frequency of the waveform category. Principal component (PC) analysis showed that PC1 was related to frequency and duration, and PC2–4 were related to each waveform. In the comparison of USV patterns and behaviors among strains, wild-derived KJR mice displayed the highest scores for PC2–4, and female mice paired with KJR males did not emit rejection-related click sounds. It is assumed that the waveforms emitted by KJR males have a positive effect in male–female interaction. Therefore, we extracted waveforms in PC2–4 from the USV recordings of KJR mice to produce a sound file, "HIGH2-4". As a negative control, another sound file ("LOW2-4") was created by extracting waveforms in PC2-4 from strains with low scores for these components. In the playback experiments using these sound files, female mice were attracted to the speaker that played HIGH2-4 but not the speaker that played LOW2-4. These results highlight the role of strain differences in the waveforms of male USVs during male–female interaction. The results indicated that female mice use male USVs as information when selecting a suitable mate

    Epstein-Barr Virus LMP2A Reduces Hyperactivation Induced by LMP1 to Restore Normal B Cell Phenotype in Transgenic Mice

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    Epstein-Barr virus (EBV) latently infects most of the human population and is strongly associated with lymphoproliferative disorders. EBV encodes several latency proteins affecting B cell proliferation and survival, including latent membrane protein 2A (LMP2A) and the EBV oncoprotein LMP1. LMP1 and LMP2A signaling mimics CD40 and BCR signaling, respectively, and has been proposed to alter B cell functions including the ability of latently-infected B cells to access and transit the germinal center. In addition, several studies suggested a role for LMP2A modulation of LMP1 signaling in cell lines by alteration of TRAFs, signaling molecules used by LMP1. In this study, we investigated whether LMP1 and LMP2A co-expression in a transgenic mouse model alters B cell maturation and the response to antigen, and whether LMP2A modulates LMP1 function. Naïve LMP1/2A mice had similar lymphocyte populations and antibody production by flow cytometry and ELISA compared to controls. In the response to antigen, LMP2A expression in LMP1/2A animals rescued the impairment in germinal center generation promoted by LMP1. LMP1/2A animals produced high-affinity, class-switched antibody and plasma cells at levels similar to controls. In vitro, LMP1 upregulated activation markers and promoted B cell hyperproliferation, and co-expression of LMP2A restored a wild-type phenotype. By RT-PCR and immunoblot, LMP1 B cells demonstrated TRAF2 levels four-fold higher than non-transgenic controls, and co-expression of LMP2A restored TRAF2 levels to wild-type levels. No difference in TRAF3 levels was detected. While modulation of other TRAF family members remains to be assessed, normalization of the LMP1-induced B cell phenotype through LMP2A modulation of TRAF2 may be a pathway by which LMP2A controls B cell function. These findings identify an advance in the understanding of how Epstein-Barr virus can access the germinal center in vivo, a site critical for both the genesis of immunological memory and of virus-associated tumors

    Inherited liver shunts in dogs elucidate pathways regulating embryonic development and clinical disorders of the portal vein

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    Congenital disorders of the hepatic portal vasculature are rare in man but occur frequently in certain dog breeds. In dogs, there are two main subtypes: intrahepatic portosystemic shunts, which are considered to stem from defective closure of the embryonic ductus venosus, and extrahepatic shunts, which connect the splanchnic vascular system with the vena cava or vena azygos. Both subtypes result in nearly complete bypass of the liver by the portal blood flow. In both subtypes the development of the smaller branches of the portal vein tree in the liver is impaired and terminal branches delivering portal blood to the liver lobules are often lacking. The clinical signs are due to poor liver growth, development, and function. Patency of the ductus venosus seems to be a digenic trait in Irish wolfhounds, whereas Cairn terriers with extrahepatic portosystemic shunts display a more complex inheritance. The genes involved in these disorders cannot be identified with the sporadic human cases, but in dogs, the genome-wide study of the extrahepatic form is at an advanced stage. The canine disease may lead to the identification of novel genes and pathways cooperating in growth and development of the hepatic portal vein tree. The same pathways likely regulate the development of the vascular system of regenerating livers during liver diseases such as hepatitis and cirrhosis. Therefore, the identification of these molecular pathways may provide a basis for future proregenerative intervention

    Age-Related Impairment of Ultrasonic Vocalization in Tau.P301L Mice: Possible Implication for Progressive Language Disorders

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    Tauopathies, including Alzheimer's Disease, are the most frequent neurodegenerative diseases in elderly people and cause various cognitive, behavioural and motor defects, but also progressive language disorders. For communication and social interactions, mice produce ultrasonic vocalization (USV) via expiratory airflow through the larynx. We examined USV of Tau.P301L mice, a mouse model for tauopathy expressing human mutant tau protein and developing cognitive, motor and upper airway defects.At age 4-5 months, Tau.P301L mice had normal USV, normal expiratory airflow and no brainstem tauopathy. At age 8-10 months, Tau.P301L mice presented impaired USV, reduced expiratory airflow and severe tauopathy in the periaqueductal gray, Kolliker-Fuse and retroambiguus nuclei. Tauopathy in these nuclei that control upper airway function and vocalization correlates well with the USV impairment of old Tau.P301L mice.In a mouse model for tauopathy, we report for the first time an age-related impairment of USV that correlates with tauopathy in midbrain and brainstem areas controlling vocalization. The vocalization disorder of old Tau.P301L mice could be, at least in part, reminiscent of language disorders of elderly suffering tauopathy

    Skin Lesions on Common Bottlenose Dolphins (Tursiops truncatus) from Three Sites in the Northwest Atlantic, USA

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    Skin disease occurs frequently in many cetacean species across the globe; methods to categorize lesions have relied on photo-identification (photo-id), stranding, and by-catch data. The current study used photo-id data from four sampling months during 2009 to estimate skin lesion prevalence and type occurring on bottlenose dolphins (Tursiops truncatus) from three sites along the southeast United States coast [Sarasota Bay, FL (SSB); near Brunswick and Sapelo Island, GA (BSG); and near Charleston, SC (CHS)]. The prevalence of lesions was highest among BSG dolphins (P = 0.587) and lowest in SSB (P = 0.380), and the overall prevalence was significantly different among all sites (p<0.0167). Logistic regression modeling revealed a significant reduction in the odds of lesion occurrence for increasing water temperatures (OR = 0.92; 95%CI:0.906–0.938) and a significantly increased odds of lesion occurrence for BSG dolphins (OR = 1.39; 95%CI:1.203–1.614). Approximately one-third of the lesioned dolphins from each site presented with multiple types, and population differences in lesion type occurrence were observed (p<0.05). Lesions on stranded dolphins were sampled to determine the etiology of different lesion types, which included three visually distinct samples positive for herpesvirus. Although generally considered non-fatal, skin disease may be indicative of animal health or exposure to anthropogenic or environmental threats, and photo-id data provide an efficient and cost-effective approach to document the occurrence of skin lesions in free-ranging populations

    Hidden Markov models and mouse ultrasonic vocalizations

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    (a) B6 mice differentially approached socially conditioned cues relative to novel cues (*orthogonal contrast for social approach vs

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    <p><b>Copyright information:</b></p><p>Taken from "Social reward among juvenile mice"</p><p></p><p>Genes, Brain, and Behavior 2007;6(7):661-671.</p><p>Published online Jan 2007</p><p>PMCID:PMC2040181.</p><p>© 2006 The Authors Journal compilation</p> novelty approach, = 0.03, social approach = time in social environment time in novel environment). (b) Unconditioned B6 mice did not respond differentially to the presentation of novel cues in the testing arena (novelty approach = time in novel environment time in familiar environment). (c) B6 mice approached novel environments only when the other peripheral compartment of the testing arena contained cues that predicted social isolation (orthogonal contrast for isolation aversion vs. novelty approach, < 0.001, isolation aversion = time in novel environment time in isolate environment). Data in each panel are presented as the mean ± SEM

    (a–c) Frequency distributions illustrate the number of mice (ordinate) expressing a particular preference score (abscissa) following (a) no conditioning, (b) social conditioning or (c) food conditioning

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    <p><b>Copyright information:</b></p><p>Taken from "Social reward among juvenile mice"</p><p></p><p>Genes, Brain, and Behavior 2007;6(7):661-671.</p><p>Published online Jan 2007</p><p>PMCID:PMC2040181.</p><p>© 2006 The Authors Journal compilation</p> Mice from all of the strains were included in the distributions. (a′–c′) Juvenile mice did not differentially approach or explore the environments (a′) without conditioning. (b′) Social conditioning resulted in a CPP for mice from three strains but not BALB mice (Tukey’s HSD tests, * < 0.05 for all tests comparing BALB with the other strains). (c′) Mice from all of the strains learned the conditioning contingency when food was used as a reward. Preference scores were calculated as the duration spent in the reward-paired (social or food) environment the duration spent in the reward-impoverished (isolation or food deprivation) environment. (a″–c″) There were strain-dependent differences in locomotor activity (a″) without conditioning, (b″) with social conditioning and (c″) with food conditioning. There was no difference in exploratory activity between BALB and B6 mice that were tested following the food conditioning procedure (Tukey’s HSD tests, * < 0.05 compared with all other strains, < 0.05 compared with the A strain, < 0.05 compared with the A and DBA strains). Data in panels a′–c′ and a″–c″ are presented as the mean ± SEM
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