Importing genetically altered animals: ensuring quality.

The reproducibility of research using laboratory animals requires reliable management of their quality, in particular of their genetics, health and environment, all of which contribute to their phenotypes. The point at which these biological materials are transferred between researchers is particularly sensitive, as it may result in a loss of integrity of the animals and/or their documentation. Here, we describe the various aspects of laboratory animal quality that should be confirmed when sharing rodent research models. We also discuss how repositories of biological materials support the scientific community to ensure the continuity of the quality of laboratory animals. Both the concept of quality and the role of repositories themselves extend to all exchanges of biological materials and all networks that support the sharing of these reagents.

Towards large scale automated cage monitoring - Diurnal rhythm and impact of interventions on in-cage activity of C57BL/6J mice recorded 24/7 with a non-disrupting capacitive-based technique.

BACKGROUND AND AIMS: Automated recording of laboratory animal's home cage behavior is receiving increasing attention since such non-intruding surveillance will aid in the unbiased understanding of animal cage behavior potentially improving animal experimental reproducibility. MATERIAL AND METHODS: Here we investigate activity of group held female C57BL/6J mice (mus musculus) housed in standard Individually Ventilated Cages across three test-sites: Consiglio Nazionale delle Ricerche (CNR, Rome, Italy), The Jackson Laboratory (JAX, Bar Harbor, USA) and Karolinska Insititutet (KI, Stockholm, Sweden). Additionally, comparison of female and male C57BL/6J mice was done at KI. Activity was recorded using a capacitive-based sensor placed non-intrusively on the cage rack under the home cage collecting activity data every 250 msec, 24/7. The data collection was analyzed using non-parametric analysis of variance for longitudinal data comparing sites, weekdays and sex. RESULTS: The system detected an increase in activity preceding and peaking around lights-on followed by a decrease to a rest pattern. At lights off, activity increased substantially displaying a distinct temporal variation across this period. We also documented impact on mouse activity that standard animal handling procedures have, e.g. cage-changes, and show that such procedures are stressors impacting in-cage activity. These key observations replicated across the three test-sites, however, it is also clear that, apparently minor local environmental differences generate significant behavioral variances between the sites and within sites across weeks. Comparison of gender revealed differences in activity in the response to cage-change lasting for days in male but not female mice; and apparently also impacting the response to other events such as lights-on in males. Females but not males showed a larger tendency for week-to-week variance in activity possibly reflecting estrous cycling. CONCLUSIONS: These data demonstrate that home cage monitoring is scalable and run in real time, providing complementary information for animal welfare measures, experimental design and phenotype characterization.

Mobile technology use and skills among individuals with fragile X syndrome: implications for healthcare decision making.

BACKGROUND: Little is known about how individuals with fragile X syndrome (FXS) and their families use technology in daily life and what skills individuals with FXS can perform when using mobile technologies. METHODS: Using a mixed-methods design, including an online survey of parents (n = 198) and a skills assessment of individuals with FXS (n = 6), we examined the experiences and abilities of individuals with FXS for engaging with mobile technology. RESULTS: Parents reported that individuals with FXS often used technology in their daily lives, with variations based on age of child, sex, autism status, depression, and overall ability. Parents frequently sought and shared FXS-related information online. Assessment data revealed that individuals with FXS demonstrated proficiency in interacting with technology. CONCLUSIONS: Mobile technology is a tool that can be used in FXS to build skills and increase independence rather than simply for recreational purposes. Implications for using mobile technology to enhance healthcare decision making are discussed.

Validity of a condition specific outcome measure for fragile X syndrome: the Aberrant Behaviour Checklist-utility index.

BACKGROUND: The purpose of this study was to assess the construct validity of the Aberrant Behaviour Checklist-utility index (ABC-UI) by examining the relationship between healthcare resource utilisation by patients with fragile X syndrome (FXS) as well as burden experienced by their caregivers. METHOD: In 2011, a total of 350 US caregivers of individuals with FXS completed a questionnaire that captured information on FXS-related burden as well as the ABC-Community. Using the ABC-UI, a condition-specific outcome measure derived from the ABC-Community, five utility index categories were created: very low (0.00-0.33); low (0.34-0.66); moderate (0.67-0.77); high (0.78-0.89); and very high (0.90-1.00). Multivariable regression models examined the association between the utility value and nine burden-related outcomes. RESULTS: Approximately 2% of individuals with FXS were in the very low utility index category, 31% low, 27% moderate, 38% high and 3% very high. The median utility value was 0.74. Women with FXS and adults 18 years and older had higher values. Regression results indicate that individuals with higher utility values were more likely to have fewer specialist visits, use fewer prescription medications, need fewer hours of unpaid caregiving, inflict fewer caregiver injuries and have caregivers with fewer mental health provider visits. CONCLUSIONS: The ABC-UI appears to function well as condition-specific outcome measure, and as an indicator of health-related quality-of-life and economic burden in individuals with FXS. Among patients with FXS in the US and their caregivers, significant differences in health care resource utilisation and burden exist across health state utility categories.

Aggression in fragile X syndrome.

BACKGROUND: Individuals with fragile X syndrome (FXS), especially men, have long been described as presenting with significant behavioural challenges. Despite this known aspect of the phenotype, there has been little research exploring the prevalence, frequency, nature or consequences of aggressive behaviour in FXS. METHODS: This study used survey methodology to gather caregiver reports on the types, frequency and severity of aggressive behaviour in 774 individuals with FXS. RESULTS: Based on caregiver report, nearly all (>90%) male and female individuals were reported to have engaged in some aggression over the previous 12 months, with a third of male cases and slightly fewer than 20% of female cases being described as engaging in moderate to severe aggression or being diagnosed or treated for aggression. Further, aggressive behaviours in male individuals were serious enough that 30% had caused injuries to caregivers and 22% had caused injuries to peers or friends. Sensory issues and hyperactivity were significant predictors of the frequency of aggressive acts, while sensory issues and anxiety were predictive of the severity of aggression. Traditional behaviour management techniques as well as medication was described as the most common and successful treatment options. CONCLUSIONS: Aggressive behaviours are a significant concern for a subsample of both male and female individuals with FXS. Given that sensory concerns were predictive of both the frequency and the severity of aggression suggests these behaviours may be a reactive means of escaping uncomfortable situations.

FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units.

The microbiological quality of experimental animals can critically influence animal welfare and the validity and reproducibility of research data. It is therefore important for breeding and experimental facilities to establish a laboratory animal health monitoring (HM) programme as an integrated part of any quality assurance system. FELASA has published recommendations for the HM of rodent and rabbit colonies in breeding and experimental units (Nicklas et al. Laboratory Animals, 2002), with the intention of harmonizing HM programmes. As stated in the preamble, these recommendations need to be adapted periodically to meet current developments in laboratory animal medicine. Accordingly, previous recommendations have been revised and shall be replaced by the present recommendations. These recommendations are aimed at all breeders and users of laboratory mice, rats, Syrian hamsters, guinea pigs and rabbits as well as diagnostic laboratories. They describe essential aspects of HM, such as the choice of agents, selection of animals and tissues for testing, frequency of sampling, commonly used test methods, interpretation of results and HM reporting. Compared with previous recommendations, more emphasis is put on the role of a person with sufficient understanding of the principles of HM, opportunistic agents, the use of sentinel animals (particularly under conditions of cage-level containment) and the interpretation and reporting of HM results. Relevant agents, testing frequencies and literature references are updated. Supplementary information on specific agents and the number of animals to be monitored and an example of a HM programme description is provided in the appendices.

Report of the Federation of European Laboratory Animal Science Associations Working Group on animal identification.

The primary aim of this report is to assist scientists in selecting more reliable/suitable identification (ID) methods for their studies. This is especially true for genetically altered (GA) animals where individual identification is strictly necessary to link samples, research design and genotype. The aim of this Federation of European Laboratory Animal Science Associations working group was to provide an update of the methods used to identify rodents in different situations and to assess their implications for animal welfare. ID procedures are an indispensable prerequisite for conducting good science but the degree of invasiveness differs between the different methods; therefore, one needs to make a good ethical evaluation of the method chosen. Based on the scientific literature the advantages and disadvantages of various methods have been presented comprehensively and this report is intended as a practical guide for researchers. New upcoming methods have been included next to the traditional techniques. Ideally, an ID method should provide reliable identification, be technically easy to apply and not inflict adverse effects on animals while taking into account the type of research. There is no gold standard method because each situation is unique; however, more studies are needed to better evaluate ID systems and the desirable introduction of new and modern approaches will need to be assessed by detailed scientific evaluation.

Therapy service use among individuals with fragile X syndrome: findings from a US parent survey.

BACKGROUND: Fragile X syndrome (FXS) is known to be associated with a range of developmental challenges, yet the occurrence and intensity of therapy services along with associated factors have not been determined. METHOD: In a US national survey, caregivers provided information regarding the therapy services received by their sons (n = 1013) and daughters (n = 283) with FXS (from birth to 63 years; mean = 15.6 years, SD = 10.6). Caregivers reported (1) type, (2) amount, (3) location, and (4) overall satisfaction with services. Associations with other child variables and family income were also examined. RESULTS: Key findings included that 72% of males and 47% of females were currently receiving at least one type of therapy service; the most common services for both males and females were speech-language therapy (ST) and occupational therapy (OT). Overall, males were more likely to receive therapy services as well as a greater number of services than females. Autism status was significantly associated with both males and females receiving ST and males receiving OT and behaviour management therapy. Therapies were provided in a variety of locations, and parents were generally satisfied with the amount and quality of therapy services. Age-related declines were evident in the use of services for both males and females, with very few individuals receiving any therapy services after 20 years of age. CONCLUSIONS: This study provides a baseline description of the current state of therapy services for children with FXS, laying a foundation for future research and recommendations for service provision and policy.

Employment impact and financial burden for families of children with fragile X syndrome: findings from the National Fragile X Survey.

BACKGROUND: The employment impact and financial burden experienced by families of children with fragile X syndrome (FXS) has not been quantified in the USA. METHOD: Using a national fragile X family survey, we analysed data on 1019 families with at least one child who had a full FXS mutation. Out-of-pocket expenditures related to fragile X were reported. We used logistic regression to examine the role of insurance, number of affected children, and number of total co-occurring conditions in predicting the financial burden and employment impact of FXS, while adjusting for race, education, marital status and other sociodemographic predictors. RESULTS: Almost half of families affected by FXS reported that they had experienced an increased financial burden and nearly 60% stated that they had had to change work hours or stop work because of FXS. Families with health insurance that met family needs were significantly less likely to report an excess financial burden. The type of insurance (private or public) was not associated with the reported financial burden. Affected children's mutation status, especially male children with the full mutation, was associated with employment impact. The total number of co-occurring conditions was associated with both financial burden and employment impact. CONCLUSIONS: Families affected by FXS experienced a significant employment impact and financial burden. Policies designed to help families with FXS need to take into consideration the dimension of co-occurring conditions.

An impending crisis in the provision of histopathology expertise for mouse functional genomics.

The generation of new mouse models of human disease is accelerating rapidly, due to the completion of whole-genome sequencing efforts and technological advances in the manipulation of the mouse genome. We sought to investigate manpower issues in the provision of histopathology expertise for mouse functional genomics and compared this to the perceived demand from principal investigators (PIs). Through the European Commission (EC)-funded PRIME pathology training initiative, two questionnaires were devised to collect information from pathologists and EC-funded PIs on the current provision of mouse histopathology expertise in Europe and the demands for this service. We find that pathological analysis is being performed almost exclusively by professionally qualified pathologists, generally employed in clinical diagnostic posts, where the work is undertaken as collaboration outside of their contractual commitments but without previous training in veterinary or comparative pathology. The results indicate that there is a lack of both trainees and provision of specialist training in this field. Unsurprisingly, the availability of diagnostic expertise and advice falls far short of the number of genetically engineered mice (GEM) being generated for analysis. We analyse these results with reference to previous studies and discuss solutions for the future recruitment, training and funding for pathologists in mouse functional genomics in Europe.

Oral-facial-digital type 1 syndrome of Papillon-Léage and Psaume.

A female infant was classified as having oral-facial-digital syndrome (OFDS) type 1, with oral (cleft palate, bifid uvula, lingual cleft, numerous hypertrophic frenula), facial (numerous milia on face, scalp, and ears; frontal bossing; hypertelorism; hypoplasia of nasal alar cartilage; micrognathia), and digital (bilateral brachydactyly of hands) symptoms. She also had diffuse, nonscarring alopecia with wiry, dry hair. Results of roentgenographic and ultrasound studies were normal. At her present age of 11 months, her psychomotor development is appropriate for her age.