Behavior of Lurcher Mice and Wild Type Mice
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The document summarizes several experiments conducted to analyze the behavior of Lurcher mutant mice compared to wild type mice. Tests included the wooden beam test to measure balance and coordination, the hole board test to assess exploratory behavior, and general activity and grooming tests. Results showed Lurcher mice had poorer motor coordination on the wooden beam test and higher hind limb usage in mobility tests compared to wild type mice. Several research papers are cited relating to motor deficits and abnormalities observed in Lurcher mice.
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Behavior of Lurcher Mice and Wild Type Mice
- 1. Behavior of Lurcher mutants and wild type mice Evelyn Lee Goldy Landau
- 2. Wooden Beam Results For a single trial, each animal will be placed at the middle of the beam. The number of crossings, the time spent on the beam before falling, and the number of paw slips will be recorded for a maximum of 60 seconds (e.g. if a mouse falls after 5 sec, the time spent on beam = 5 sec and trial ends) This shows the slips per minute in our tests.
- 3. Wooden Beam Test: A small wooden beam (2 cm in diameter) and a larger steel beam (3.5 cm in diameter), each 1 m in length, were separated into 10-cm segments by felt pen line markings and placed at a height of 60 cm from a cushioned-covered floor. Wooden Beam Test - Literature
- 4. Hole Board Test Results
- 7. ● Motor Task (Suspension) ○ 2mm bar ○ 4mm bar ● Sensory Task (Negative Geotaxis) ○ vestibular system ○ Y/N Neurological Testing
- 8. Results ● There was significantly higher number of hind limb usage in Group B mice than in Group A.
- 9. ● “Motor Abnormalities in Lurcher Mutant Mice” ○ Lalonde et al. ○ Coat hanger test ○ Normal Lurcher ● "In the coat-hanger test, lurcher mutants showed inferior performance” Literature
- 10. ● Motor coordination in mice with hotfoot, Lurcher, and double mutations of the Grid2 gene encoding the delta-2 excitatory amino acid receptor. Literature
- 12. Results
- 13. ● Grooming ○ Occur both in high stress and low stress environment ■ comfort; transition from rest to activity ■ frequent bursts of rapid short grooming ○ Cephalocaudal progression ■ head→ body → tail Literature
- 14. Literature
- 15. ● Greer, Capecchi. (2002) Hoxb8 Is Required for Normal Grooming Behavior in Mice. Neuron. Vol 33, Issue 1. pp. 23-24 ● Kaleueff. (2004). Grooming analysis algorithm for neurobehavioural stress research. Brain Research Protocols. Vol 13, Issue 3. pp. 151-158 ● Lalonde et al. (2003). Motor Coordination in Mice with Hotfoot, Lurcher, and Double Mutations of the Grid2 Gene Encoding the Delta-2 Excitatory Amino Acid Receptor. Physiology & Behavior. Vol 80. pp. 333-9 ● Lalonde et al. (1992). Motor Abnormalities in Lurcher Mutant. Physiology & Behavior. Vol 51. pp. 523-525 Bibliography
Notas del editor
- Results of our experiments - Discussion of results in light of the literature
- Goldy Average forepaw slips (p<0.05)
- Goldy On the small wooden beam, the three groups differed for number of segments traversed [F(2,29)=16.63, P<.001], latencies before falling [F(2,29)=26.93, P<.001], and number of falls [F(2,29)=27.27, P<.001]. As seen in Table 1, the number of segments traversed by Grid2ho/Lc and Grid2ho/ho groups did not differ from each other, but each had lower values than the nonataxic Grid2ho/+ group (P<.001). For latencies before falling and falls, Grid2ho/Lc double mutants had lower values than Grid2ho/ho single mutants, which in turn had lower values than Grid2ho/+ nonataxic heterozygotes (P<.01). On the larger steel beam (Table 1), the three groups once again differed for number of segments traversed [F(2,29)=16.56, P<.001], latencies before falling [F(2,29)=34.87, P<.001], and number of falls, [F(2,29)=28.62, P<.001]. For every measure, the number of segments traversed by Grid2ho/Lc and Grid2ho/ho was each lower than that of Grid2ho/+ (P<.001). However, there was no difference between Grid2ho/Lc and Grid2ho/ho (P±.05).
- Goldy
- Evelyn In the motor task, we let mice hold onto the bar of 2mm and 4mm diameter. Then, we suspended it ~40cm above the ground and the time until it looses the grip and fall down was measured For the sensory task, place mouse on the grid horizontally, turn the grid to vertical orientation and assess ability to face upwards.
- Evelyn p<0.01
- Evelyn In this literature, they performed a coat hanger task, where they put the mouse in the middle of the coat hanger, and measured the time until it loosened its grip and touched the side bar.
- Evelyn ho/+ : non-ataxic Grid2ho/Lc double mutant did not differ from Grid2Lc/+ mice Grid2ho/Lc and Grid2ho/ho fell sooner and more often than Grid2ho/+
- Evelyn AMB,total,: not significant central square entries: not sig grooming: lowest p number (p=0.167) but still not significant observation: grooming excessively.
- Evelyn few sample
- need to summarize below: Grooming is an innate behavior that is represented across most animal species, including humans (Sachs, 1988). Care of one's own body surface, autogrooming, is a spontaneous behavior that generally occurs as a transition behavior between periods of rest and activity (Fentress, 1988). During grooming bouts in rodents, and many other mammalian species, a general pattern of cephalocaudal progression is observed, i.e., the head is groomed first, followed by the body region, and finally the anogenital region and tail. The most highly predictable stereotyped action sequence is described as an “idealized syntactic grooming chain” (Berridge et al., 1987). Analysis of grooming behaviors in rodents suggests that pattern-generating signals originating within the CNS organize the physical movements performed during individual grooming bouts Berridge et al. 1987, Berridge and Whishaw 1992 and Richmond and Sachs 1980. Multiple regions of the brain, but most notably the brainstem and striatum, appear to be involved in implementing the syntactic grooming chain Aldridge et al. 1993, Berntson et al. 1988, Berridge 1989a and Berridge and Whishaw 1992. Obsessive-compulsive disorder (OCD) in humans is a condition that is often characterized by excessive behaviors dealing with cleanliness, including grooming. Epidemiological studies using cross-national representations have indicated that this disorder is quite common in humans, with a prevalence rate ranging from 1.9–2.5 per 100 in seven separate international communities (Horwath and Weissman, 2000). However, genes that influence this complex behavior have yet to be identified. In this context, it is of particular interest that mice homozygous for a loss-of-function mutation in Hoxb8 show excessive pathological grooming behavior, leading to hair removal and self-inflicted wounds at over-groomed sites. --- Self-grooming is an ancient innate behaviour that is represented across most animal species [19] and is a particularly important part of rodent behavioural repertoire [2], [3], [4], [5] and [29]. In rodents, a general pattern of self-grooming cephalocaudal progression is observed as follows: paw licking, nose and face wash, head wash, body wash and fur licking, leg licking, tail/genitals licking and wash [5], [14], [15] and [26]. Many neuromediators and hormones as well as multiple regions in the brain appear to be involved in the regulation of self-grooming behaviours [2], [3], [6], [7], [11], [13], [28] and [29]. Grooming is also known to be bidirectionally sensitive to various psychotropic drugs and genetic manipulations [12], [13] and [21], and is often studied in mice [6], [18], [19] and [27]. It has long been known that rodents' grooming activity can be generally increased in two opposite situations: in high and low stress [20], [21] and [24]. Low-stress comfort grooming is a spontaneous body care ritual which occurs as a transition from rest to activity; it is a typical behavioural marker of low or no stress and usually goes in a “relaxed fashion” from paw licking to tail/genitals wash [17], [20] and [21]. Similarly, stress has long been known to induce grooming in rodents [14], [25] and [28]. However, this stress-evoked grooming is ethologically different from low-stress grooming, and characterised by frequent bursts of rapid short grooming [17], [25] and [28]. we wanted to know if our protocol can be used to assess grooming behaviours in mutant mice. Using “anxious” mice lacking neurosteroid vitamin D receptor (VDR) gene [22] as an example, we demonstrated that our algorithm is able to detect stress-evoked differences in grooming of genetically modified animals. Overall, in the present study we show that the protocol allows detection of stress by measuring alterations in grooming patterns (microstructure), and could be extensively used in neurobehavioural stress research and behavioural phenotyping of genetically modified animals.
- elevated plus maze: high stress model NB- number of grooming; GD- total duration of grooming; TT- number of transitions between grooming stages