A Molecular Investigation of Inbreeding in Captive Addra Gazelles

Captive breeding of individuals to augment or reestablish a wild population requires the maintenance of maximum possible genetic variation to reflect the genetic variation present in the original wild population and reduce the occurrence of genetic drift or inbreeding in the captive population. Critically threatened addra gazelles (Nanger dama ruficollis) have been maintained in a captive breeding program since 1969 (10-15 generations) with no introduction of genetic material beyond the original 22 founders, of which only 8 have recorded descendents in the current population. Results from this study show a strong relationship between infant mortality and inbreeding, and a substantial increase in infant mortality over the first 20 years of the breeding program. In addition, molecular measures of inbreeding were correlated to various historical scenarios and suggest that more founders may have contributed to the population than expected based on pedigree data alone. A genetic sampling of all individuals in the population may be the only way to identify the most genetically distinct individuals in the population, and the best option for maintaining future genetic diversity

Cognitive dysfunction precedes the onset of motor symptoms in the MitoPark mouse model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder primarily characterized by progressive loss of dopamine neurons, leading to loss of motor coordination. However, PD is associated with a high rate of non-motor neuropsychiatric comorbities that often develop before the onset of movement symptoms. The MitoPark transgenic mouse model is the first to recapitulate the cardinal clinical features, namely progressive neurodegeneration and death of neurons, loss of motor function and therapeutic response to L-DOPA. To investigate whether MitoPark mice exhibit early onset of cognitive impairment, a non-motor neuropsychiatric comorbidity, we measured performance on a spatial learning and memory task before (∼8 weeks) or after (∼20 weeks) the onset of locomotor decline in MitoPark mice or in littermate controls. Consistent with previous studies, we established that a progressive loss of spontaneous locomotor activity began at 12 weeks of age, which was followed by progressive loss of body weight beginning at 16-20 weeks. Spatial learning and memory was measured using the Barnes Maze. By 20 weeks of age, MitoPark mice displayed a substantial reduction in overall locomotor activity that impaired their ability to perform the task. However, in the 8-week-old mice, locomotor activity was no different between genotypes, yet MitoPark mice took longer, traveled further and committed more errors than same age control mice, while learning to successfully navigate the maze. The modest between-day learning deficit of MitoPark mice was characterized by impaired within-day learning during the first two days of testing. No difference was observed between genotypes during probe trials conducted one or twelve days after the final acquisition test. Additionally, 8-week-old MitoPark mice exhibited impaired novel object recognition when compared to control mice. Together, these data establish that mild cognitive impairment precedes the loss of motor function in a novel rodent model of PD, which may provide unique opportunities for therapeutic development

Progressive loss of body weight and motor function in MitoPark mice.

<p>(A) Body weights were recorded weekly in either MitoPark mice or their wild-type phenotype littermate controls. (B) Horizontal and (C) vertical locomotor activity were measured at the indicated times in both MitoPark mice or their wild-type phenotype littermate control mice. Data represent mean ± SEM, (n = 10 mice/group). Significant post hoc effect indicated (*p<0.05) for MitoPark versus same time point littermate controls.</p

Behavior was assessed during a single probe trial 24 hours after the final day 4 training trial.

<p>The (A) latency to locate the correct target hole, (B) velocity during the trial, (C) distance traveled to locate the target hole and (D) the total number of sampling errors committed during the trial were measured in 8 week old MitoPark or wild-type phenotype littermate control mice. (E) The duration of time spent in each of ten identical virtual zones (schematic in F) around the perimeter of the maze was recorded, and (F) the distribution of sampling errors was recorded. Dashed lines represent the theoretical threshold if exploratory behavior were random. Data represent mean ± SEM, (n = 8 mice/group).</p