Evaluation of tarsal injuries in C57BL/6J male mice.

Tarsal joint abnormalities have been observed in aged male mice on a C57BL background. This joint disease consists of calcaneal displacement, inflammation, and proliferation of cartilage and connective tissue, that can progress to ankylosis of the joint. While tarsal pathology has been described previously in C57BL/6N substrains, as well as in STR/ort and B10.BR strain, no current literature describes this disease occurring in C57BL/6J mice. More importantly the behavioral features that may result from such a change to the joint have yet to be evaluated. This condition was observed in older male mice of the C57BL/6J lineage, around the age of 20 weeks or older, at a frequency of 1% of the population. To assess potential phenotypic sequela, this study sought to evaluate body weight, frailty assessment, home cage wheel running, dynamic weight bearing, and mechanical allodynia with and without the presence of pain relief with morphine. Overall mice with tarsal injuries had significantly higher frailty scores (p< 0.05) and weighed less (p<0.01) compared to unaffected mice. Affected mice had greater overall touch sensitivity (p<0.05) and they placed more weight on their forelimbs (p<0.01) compared to their hind limbs. Lastly, when housed with a running wheel, affected mice ran for a shorter length of time (p<0.01) but tended to run a greater distance within the time they did run (p<0.01) compared to unaffected mice. When tested just after being given morphine, the affected mice performed more similarly to unaffected mice, suggesting there is a pain sensation to this disease process. This highlights the importance of further characterizing inbred mouse mutations, as they may impact research programs or specific study goals.

Readiness for the aging population in private dental practices.

Background: As more adults reach advanced age with natural teeth, there is an increasing need for dental and dental hygiene practices to provide care for older adults and individuals living with dementia. Little is known about how well these populations are accommodated in private practice. Methods: Following approval from the Research Ethics Board at Mount Allison University, a survey was sent to the 517 practising dental hygienists in New Brunswick, Canada. They were asked to rate on 5-point scales their geriatric oral care knowledge, their willingness to receive more education on the topic, and how frequently they adjusted their care provision to meet the needs of older (age 70+) clients and those living with dementia. Results: A total of 121 dental hygienists responded (23.4% response rate). Overall, respondents were willing to learn more about geriatric care, but lacked knowledge about the oral health effects of certain medications frequently used by older adults, and about techniques for accessing the oral cavity of clients with dementia. Many accommodations recommended by geriatric specialists were not consistently carried out. Discussion: Given that older adults and adults with dementia make up an increasingly large part of the population in need of oral care, geriatric and dementia oral care needs should be emphasized in dental and dental hygiene practices and continuing education for dental hygienists. Conclusion: More research is required on the impact of integrating accommodations for older clients and clients with dementia into clinical practice, as well as how oral care is experienced by these populations.

Contexte: Un plus grand nombre d'adultes ont toujours leurs dents naturelles lorsqu'ils atteignent un âge avancé. Il est donc de plus en plus nécessaire que les cabinets dentaires et d'hygiène dentaire fournissent des soins aux personnes plus âgées et aux personnes atteintes de démence. On ignore dans quelle mesure ces populations sont accueillies dans les cabinets privés. Méthodologie: À la suite de l'approbation du comité d'éthique de la recherche de l'Université Mount Allison, un sondage a été envoyé aux 517 hygiénistes dentaires en exercice au Nouveau-Brunswick, Canada. Ils ont été invités à évaluer, sur une échelle de 5 points, leurs connaissances en matière de soins buccodentaires gériatriques, leur intérêt à recevoir davantage de formation sur le sujet et la fréquence à laquelle ils ont adapté leur prestation de soins pour répondre aux besoins des clients plus âgés (70 ans et plus) et des personnes atteintes de démence. Résultats: En tout, 121 hygiénistes dentaires ont répondu au sondage (un taux de réponse de 23,4 %). Dans l'ensemble, les répondants voulaient en savoir davantage sur les soins gériatriques, mais ne connaissaient pas les effets sur la santé buccodentaire de certains médicaments fréquemment utilisés par les personnes âgées ni les techniques utilisées pour accéder à la cavité buccale des clients atteints de démence. De nombreux accommodements recommandés par les spécialistes en gériatrie n'ont pas été systématiquement mis en œuvre. Discussion: Les cabinets dentaires et d'hygiène dentaire et la formation continue des hygiénistes dentaires doivent souligner les besoins des adultes plus âgés et des adultes atteints de démence puisque ceux-ci représentent une part de plus en plus importante de la population nécessitant des soins buccodentaires. Conclusion: Des recherches supplémentaires sont nécessaires sur les conséquences de l'intégration des accommodements pour les clients plus âgés et les clients atteints de démence dans la pratique clinique, ainsi que sur la façon dont ces populations perçoivent les soins buccodentaires.

A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations.

We have identified a point mutation in Npc1 that creates a novel mouse model (Npc1(nmf164)) of Niemann-Pick type C1 (NPC) disease: a single nucleotide change (A to G at cDNA bp 3163) that results in an aspartate to glycine change at position 1005 (D1005G). This change is in the cysteine-rich luminal loop of the NPC1 protein and is highly similar to commonly occurring human mutations. Genetic and molecular biological analyses, including sequencing the Npc1(spm) allele and identifying a truncating mutation, confirm that the mutation in Npc1(nmf164) mice is distinct from those in other existing mouse models of NPC disease (Npc1(nih), Npc1(spm)). Analyses of lifespan, body and spleen weight, gait and other motor activities, as well as acoustic startle responses all reveal a more slowly developing phenotype in Npc1(nmf164) mutant mice than in mice with the null mutations (Npc1(nih), Npc1(spm)). Although Npc1 mRNA levels appear relatively normal, Npc1(nmf164) brain and liver display dramatic reductions in Npc1 protein, as well as abnormal cholesterol metabolism and altered glycolipid expression. Furthermore, histological analyses of liver, spleen, hippocampus, cortex and cerebellum reveal abnormal cholesterol accumulation, glial activation and Purkinje cell loss at a slower rate than in the Npc1(nih) mouse model. Magnetic resonance imaging studies also reveal significantly less demyelination/dysmyelination than in the null alleles. Thus, although prior mouse models may correspond to the severe infantile onset forms of NPC disease, Npc1(nmf164) mice offer many advantages as a model for the late-onset, more slowly progressing forms of NPC disease that comprise the large majority of human cases.

Age, experience and genetic background influence treadmill walking in mice.

The use of a treadmill to gather data for gait analysis in mice is a convenient, sensitive method to evaluate motor performance. However, evidence from several species, including mice, shows that treadmill locomotion is a novel task that is not equivalent to over ground locomotion and that may be particularly sensitive to the test environment and protocol. We investigated the effects of age, genetic background and repeated trials on treadmill walking in mice and show that these factors are important considerations in the interpretation of gait data. Specifically we report that as C57BL/6J (B6) mice age, the animals use progressively longer, less frequent strides to maintain the same walking speed. The increase is most rapid between 1 and 6 months of age and is explained, in part, by changes in size and weight. We also extended previous findings showing that repeat trials cause mice to modify their treadmill gait pattern. In a second trial B6 mice consistently walk with a shorter swing phase and greater duty factor. Also, with the shortest retest interval (3 min) mice use shorter more frequent steps but the response varies with the number and timing of trials. Finally, we compared the gait pattern of an additional seven inbred strains of mice and found significant variation in the length and frequency of strides used to maintain the same walking speed. The combined results offer the bases for further mechanistic studies and can be used to guide optimal experimental design.

Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain.

Human tibial muscular dystrophy and limb-girdle muscular dystrophy 2J are caused by mutations in the giant sarcomeric protein titin (TTN) adjacent to a binding site for the muscle-specific protease calpain 3 (CAPN3). Muscular dystrophy with myositis (mdm) is a recessive mouse mutation with severe and progressive muscular degeneration caused by a deletion in the N2A domain of titin (TTN-N2ADelta83), disrupting a putative binding site for CAPN3. To determine whether the muscular dystrophy in mutant mdm mice is caused by misregulation of CAPN3 activity, genetic crosses with CAPN3 overexpressing transgenic (C3Tg) and CAPN3 knockout (C3KO) mice were generated. Here, we report that overexpression of CAPN3 exacerbates the mdm disease, leading to a shorter life span and more severe muscular dystrophy. However, in a direct genetic test of CAPN3's role as a mediator of mdm pathology, C3KO;mdm double mutant mice showed no change in the progression or severity of disease indicating that aberrant CAPN3 activity is not a primary mechanism in this disease. To determine whether we could detect a functional deficit in titin in a non-disease state, we examined the treadmill locomotion of heterozygous +/mdm mice and detected a significant increase in stride time with a concomitant increase in stance time. Interestingly, these altered gait parameters were completely corrected by CAPN3 overexpression in transgenic C3Tg;+/mdm mice, supporting a CAPN3-dependent role for the N2A domain of TTN in the dynamics of muscle contraction.

Gait analysis detects early changes in transgenic SOD1(G93A) mice.

The effective treatment or cure of motoneuron disease will require understanding the disease processes that precede irreversible cell loss. To study these early stages, and to evaluate potential treatments in relevant animal models, requires a sensitive functional assay. To this end, we sought to determine whether the gait pattern of SOD1 transgenic mice changed prior to overt symptoms. Using a simplified video-based approach we compared the treadmill gait of C57BL/6J and B6.SOD1 transgenic mice at 8 and 10 weeks of age. B6.SOD1 mice had significantly longer stride and stance times than controls by 8 weeks. Consistent with disease progression, hindpaw measures of B6.SOD1 mice showed larger changes than front paws. Differences between control and B6.SOD1 mice increased at 10 weeks, but only because repeat testing caused habituation in control mice to a greater extent than in B6.SOD1 mice. Together the results demonstrate that simplified gait analysis is sensitive to early processes of motor system disease in mice.