Examining Intercage Transmission of : Impact of Barrier Husbandry and Cage Sanitization.

(Cm) has reemerged as a prevalent bacterial contaminant of academic research mouse colonies. A study was conducted to assess the effectiveness of husbandry and cage sanitization methods in preventing intercage transmission of Cm. To assess intercage transmission during cage change, a cage housing 2 Cm-free Swiss Webster (SW; Tac:SW) sentinel mice was placed randomly on each of 12 individually ventilated cage racks, housing cages with Cm-shedding mice, located in one of 2 animal holding rooms.

Causes Persistent Subclinical Infection and Elicits Innate and Adaptive Immune Responses in C57BL/6J, BALB/cJ and J:ARC(S) Mice Following Exposure to Shedding Mice.

(Cm) has reemerged as a moderately prevalent infectious agent in research mouse colonies. Despite its' experimental use, few studies evaluate Cm's effects on immunocompetent mice following its natural route of infection. A Cm field isolate was administered (orogastric gavage) to 8-week-old female BALB/cJ (C) mice.

Combination of Systemic and Lock-Therapies with Micafungin Eradicate Catheter-Based Biofilms and Infections Caused by and in Neutropenic Rabbit Models.

Vascular catheter-related infections, primarily caused by and , pose significant challenges due to the formation of biofilms on catheters, leading to refractory disease and considerable morbidity. We studied the efficacy of micafungin in systemic and lock therapies to eliminate catheter-based biofilms and deep tissue infections in experimental central venous catheter (CVC)-related candidemia in neutropenic rabbits. Silastic CVCs in rabbits were inoculated with 1 × 10 CFU/mL of or , establishing catheter-based biofilm, and subjected to various treatments.

Examining Intercage Transmission of : Impact of Barrier Husbandry and Cage Sanitization.

(Cm) has reemerged as a prevalent bacterial contaminant of academic research mouse colonies. A study was conducted to assess the effectiveness of husbandry and cage sanitization methods in preventing intercage transmission of Cm. To assess intercage transmission during cage change, a cage housing 2 Cm-free Swiss Webster (Tac:SW; SW) sentinel mice was placed randomly on each of 12 individually ventilated cage racks, housing cages with Cm-shedding mice, located in 1 of 2 animal holding rooms.

Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease.

CLN2 disease is a fatal, childhood autosomal recessive disorder caused by mutations in ceroid lipofuscinosis type 2 (CLN2) gene, encoding tripeptidyl peptidase 1 (TPP-1). Loss of TPP-1 activity leads to accumulation of storage material in lysosomes and resultant neuronal cell death with neurodegeneration. Genotype/phenotype comparisons suggest that the phenotype should be ameliorated with increase of TPP-1 levels to 5-10% of normal with wide central nervous system (CNS) distribution.

Positron Emission Tomography Quantitative Assessment of Off-Target Whole-Body Biodistribution of I-124-Labeled Adeno-Associated Virus Capsids Administered to Cerebral Spinal Fluid.

Based on studies in experimental animals demonstrating that administration of adeno-associated virus (AAV) vectors to the cerebrospinal fluid (CSF) is an effective route to transfer genes to the nervous system, there are increasing number of clinical trials using the CSF route to treat nervous system disorders. With the knowledge that the CSF turns over four to five times daily, and evidence in experimental animals that at least some of CSF administered AAV vectors are distributed to systemic organs, we asked: with AAV administration to the CSF, what fraction of the total dose remains in the nervous system and what fraction goes off target and is delivered systemically? To quantify the biodistribution of AAV capsids immediately after administration, we covalently labeled AAV capsids with iodine 124 (I-124), a cyclotron generated positron emitter, enabling quantitative positron emission tomography scanning of capsid distribution for up to 96 h after AAV vector administration. We assessed the biodistribution to nonhuman primates of I-124-labeled capsids from different AAV clades, including 9 (clade F), rh.

Identification of Safe and Effective Intravenous Dose of AAVrh.10hFXN to Treat the Cardiac Manifestations of Friedreich's Ataxia.

Friedreich's ataxia (FA) is a life-threatening autosomal recessive disorder characterized by neurological and cardiac dysfunction. Arrhythmias and heart failure are the main cause of premature death. From prior studies in murine models of FA, adeno-associated virus encoding the normal human frataxin gene (AAVrh.

Examination of Horizontal Transmission of in Mice to Assess Biosecurity Risks.

Mice are commonly infected with (Nb) to study their immune responses. However, biosecurity measures have not been established for housing Nb-infected mice and rats. Transmission reportedly does not occur when infected mice are cohoused with naive mice.

Pathologic copulatory lock in a genetically engineered laboratory mouse breeding pair.

A breeding pair of genetically engineered laboratory mice () presented in apparent copulatory lock (coital tie). After anesthetizing the animals, gentle traction was used to separate the pair at which point a vaginal prolapse was detected and the penis was covered with black, firm, dry crusts and noted to have a solid pale, tan, firm cylindrical mass adhering to its glans. The vaginal prolapse was reduced and the female was returned to its cage.

Mechanical Washing Prevents Transmission of Bacterial, Viral, and Protozoal Murine Pathogens from Cages.

Infectious agents have varying susceptibilities to thermal inactivation and/or mechanical removal from cages by the use of heated, pressurized water. In this study, we tested whether 5 specific infectious organisms ( [segmented filamentous bacterium (SFB)], sp., mouse norovirus (MNV), sp.

Reemergence of the Murine Bacterial Pathogen in Research Mouse Colonies.

(Cm) was detected in 2 colonies of mice with lymphoplasmacytic pulmonary infiltrates by using PCR and immunohistochemistry. This discovery was unexpected, as Cm infection had not been reported in laboratory mice since the 1940s. A Cm specific PCR assay was developed and testing implemented for the resident colonies of 8 vivaria from 3 academic institutions, 58 incoming mouse shipments from 39 academic institutions, and mice received from 55 commercial breeding colonies (4 vendors).

Assessing Elimination of Mouse Kidney Parvovirus from Cages by Mechanical Washing.

Mouse kidney parvovirus (MKPV), a newly identified parvovirus of the genus , causes inclusion body nephropathy in severely immunocompromised mice and is prevalent in research mouse colonies. As nonenveloped viruses, mammalian parvoviruses are stable and generally resist thermal inactivation; however, as a novel and highly divergent parvovirus, the thermal stability of MKPV is undefined. This study aimed to evaluate the ability of cage sanitization in a mechanical washer to eliminate MKPV.

Biology and Cellular Tropism of a Unique Astrovirus Strain: Murine Astrovirus 2.

Murine astrovirus 2 (MuAstV2) is a novel murine astrovirus recently identified in laboratory and wild mice. MuAstV2 readily transmits between immunocompetent mice yet fails to transmit to highly immunocompromised mouse strains-a unique characteristic when contrasted with other murine viruses including other astroviruses. We characterized the viral shedding kinetics and tissue tropism of MuAstV2 in immunocompetent C57BL/6NCrl mice and evaluated the apparent resistance of highly immunocompromised NOD- /NjuCrl mice to MuAstV2 after oral inoculation.

Safety of Direct Intraparenchymal AAVrh.10-Mediated Central Nervous System Gene Therapy for Metachromatic Leukodystrophy.

Metachromatic leukodystrophy, a fatal pediatric neurodegenerative lysosomal storage disease caused by mutations in the arylsulfatase A () gene, is characterized by intracellular accumulation of sulfatides in the lysosomes of cells of the central nervous system (CNS). In previous studies, we have demonstrated efficacy of AAVrh.10hARSA, an adeno-associated virus (AAV) serotype rh.

Ethmoidal meningoencephalocele in a C57BL/6J mouse.

An otherwise healthy two-month-old female C57BL/6J mouse presented with a left-sided head tilt. Differential diagnoses included idiopathic necrotizing arteritis, bacterial otitis media/interna (, , , and ), encephalitis, an abscess, neoplasia, a congenital malformation and an accidental or iatrogenic head trauma. Magnetic resonance imaging (MRI) revealed a large space-occupying right olfactory lobe intra-axial lesion with severe secondary left-sided subfalcine herniation.

Serendipitous Discovery of a Novel Murine Astrovirus Contaminating a Murine Helper T-cell Line and Incapable of Infecting Highly Immunodeficient Mice.

The unexpected seroconversion of sentinel mice in our facility to murine T lymphotrophic virus (MTLV) positivity led to our identification of a novel murine astrovirus that we designated murine astrovirus 2 (MuAstV-2). During our investigation, MuAstV-2 was found to be a contaminant of the T helper cell line (D10. G4.

Mite Burden and Immunophenotypic Response to in Swiss Webster, BALB/c, C57BL/6, and NSG Mice.

Detection methods for were historically unreliable, and testing was rarely performed because its prevalence in laboratory mice was underestimated. Although infestations are unapparent in most mouse strains, burdens are higher and clinical signs detected in various immunodeficient strains. The parasite's influence on the immune system of immunocompetent mice is unknown.

Outbreaks of Typhlocolitis Caused by Hypervirulent Group ST1 in Highly Immunocompromised Strains of Mice.

is an enteric pathogen that can cause significant clinical disease in both humans and animals. However, clinical disease arises most commonly after treatment with broad-spectrum antibiotics. The organism's ability to cause naturally occurring disease in mice is rare, and little is known about its clinical significance in highly immunocompromised mice.

Detection of in Fur Swab and Fecal Samples by Using PCR Analysis.

Current methods for detecting mites in mouse colonies have limitations in terms of cost, accuracy, and throughput. To address these limitations, we developed PCR assays to detect in fecal samples. Using a newly generated ribosomal RNA sequence of (MC28S), we developed PCR and qPCR assays capable of detecting mites or eggs ingested during grooming.

Ceftolozane-Tazobactam in the Treatment of Experimental Pseudomonas aeruginosa Pneumonia in Persistently Neutropenic Rabbits: Impact on Strains with Genetically Defined Mechanisms of Resistance.

Ceftolozane-tazobactam (C/T) is a novel cephalosporin with activity against that is resistant to extended-spectrum penicillins and antipseudomonal cephalosporins. In order to assess the antimicrobial effect of C/T in treatment of pneumonia, we investigated the pharmacokinetics and efficacy of C/T in persistently neutropenic rabbits. pneumonia was established by direct endotracheal inoculation.

Ivermectin-compounded Feed Compared with Topical Moxidectin-Imidacloprid for Eradication of in Laboratory Mice.

Demodex musculi is a prostigmatid follicular mite that has rarely been reported in laboratory mice. Although prevalence of this species has not been assessed formally, we have found that many imported mouse strains from noncommercial sources harbor Demodex mites. To assess whether an acaricide can be used to eradicate this mite, infested immunocompromised mice were provided ivermectin-compounded (12 ppm) feed without restriction for 8 wk (n = 10), were treated topically with moxidectin and imidacloprid (MI; 3 and 13 mg/kg, respectively) weekly for 8 wk (n = 10), or remained untreated (n = 10).

Comparison of Diagnostic Methods and Sampling Sites for the Detection of Demodex musculi.

Demodex mites are microscopic, cigar-shaped, follicular mites often regarded as commensal microfauna in mammals. Although Demodex spp. can cause dermatologic disease in any immunocompromised mammal, they are rarely reported in laboratory mice.

AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive degenerative neurological disorder affecting nearly one in nine elderly people in the United States. Population studies have shown that an inheritance of the apolipoprotein E (APOE) variant APOE4 allele increases the risk of developing AD, whereas APOE2 homozygotes are protected from late-onset AD. It was hypothesized that expression of the "protective" APOE2 variant by genetic modification of the central nervous system (CNS) of APOE4 homozygotes could reverse or prevent progressive neurologic damage.