| Phenotypic Profile |
| Category |
Entity |
Quantity |
Experimental Paradigm |
Age at Testing |
| Circadian sleep/wake cycle |
Locomotor activity in diurnal cycle: light phase4 |
Decreased
Description: Heterozygous females showed a moderate decline of diurnal activity compared to wildtype.
Exp Paradigm: Measurement of ambulatory behavior over a 24-hour period
|
Beam crossing |
4 months |
| |
|
Description: Heterozygous females showed a moderate decline of diurnal activity compared to wildtype.
Exp Paradigm: Measurement of ambulatory behavior over a 24-hour period |
|
|
| Motor phenotype |
Limb posture2 |
Abnormal
Description: Hindlimb clasping, which is considered an identifying characteristic of symptomatic RTT mice, was observed in approximately 70% of Mecp2 -/+ rats by 9 months of age
Exp Paradigm: General observations
|
General observations |
1-9 months |
| |
|
Description: Hindlimb clasping, which is considered an identifying characteristic of symptomatic RTT mice, was observed in approximately 70% of Mecp2 -/+ rats by 9 months of age
Exp Paradigm: General observations |
|
|
| Motor phenotype |
Gait2 |
Abnormal
Description: Mecp2 -/+ rats displayed significant deviations from wild-type motor patterns at various time points, with relatively clear trends toward alterations throughout development. Mecp2-/+ crossing speed was decreased and number of steps increased at both 6 and 9 months of age. Usage of 3-paw support during movement was decreased in Mecp2 -/+ rats at one week post-weaning as well as 12 and 15 months of age. The base of support, or width of stance, between hind paws was found to be increased in Mecp2 -/+ rats beginning at 6 months of age and continuing through 15 months of age.
Exp Paradigm: Footprint analysis: Catwalk testing
|
Footprint analysis |
1-18 months |
| |
|
Description: Mecp2 -/+ rats displayed significant deviations from wild-type motor patterns at various time points, with relatively clear trends toward alterations throughout development. Mecp2-/+ crossing speed was decreased and number of steps increased at both 6 and 9 months of age. Usage of 3-paw support during movement was decreased in Mecp2 -/+ rats at one week post-weaning as well as 12 and 15 months of age. The base of support, or width of stance, between hind paws was found to be increased in Mecp2 -/+ rats beginning at 6 months of age and continuing through 15 months of age.
Exp Paradigm: Footprint analysis: Catwalk testing |
|
|
| Motor phenotype |
Limb posture4 |
Abnormal
Description: Heterozygous females showed an increase in hind limb stance width, reflecting postural deficits
Exp Paradigm: Measurement of hind paw stance width
|
General observations |
4 months |
| |
|
Description: Heterozygous females showed an increase in hind limb stance width, reflecting postural deficits
Exp Paradigm: Measurement of hind paw stance width |
|
|
| Motor phenotype |
Gait4 |
Abnormal
Description: Heterozygous females showed abnormal gait measured by the step cycle of the forepaws: brake and swing times were increased, and the propel phase was decreased compared to wildtype. The hind paw step cycle did not show statistically significant differences.
Exp Paradigm: Measurement of DigiGait parameters: brake is the interval from first contact with surface to peak stance, propel is the phase from peak until end of contact, swing is the transitional phase in which the paw is not in contact and extends forward.
|
Gait |
4 months |
| |
|
Description: Heterozygous females showed abnormal gait measured by the step cycle of the forepaws: brake and swing times were increased, and the propel phase was decreased compared to wildtype. The hind paw step cycle did not show statistically significant differences.
Exp Paradigm: Measurement of DigiGait parameters: brake is the interval from first contact with surface to peak stance, propel is the phase from peak until end of contact, swing is the transitional phase in which the paw is not in contact and extends forward. |
|
|
| Motor phenotype |
Motor coordination and balance2 |
Decreased
Description: Mecp2 -/+ females also demonstrated a decreased latency to fall at 9 months of age compared to wild-type littermate controls.
Exp Paradigm: Footprint analysis
|
Footprint analysis |
1-9 months |
| |
|
Description: Mecp2 -/+ females also demonstrated a decreased latency to fall at 9 months of age compared to wild-type littermate controls.
Exp Paradigm: Footprint analysis |
|
|
| Motor phenotype |
General locomotor activity2 |
Decreased
Description: Mecp2 -/+ rats displayed a trend toward a decrease in distance travelled, average velocity, and time spent highly mobile, with these parameters showing genotype-specific statistical significance at only one or two time points between the age of weaning and 15 months.
Exp Paradigm: Open field test
|
Open field test |
1-15 months |
| |
|
Description: Mecp2 -/+ rats displayed a trend toward a decrease in distance travelled, average velocity, and time spent highly mobile, with these parameters showing genotype-specific statistical significance at only one or two time points between the age of weaning and 15 months.
Exp Paradigm: Open field test |
|
|
| Motor phenotype |
Ataxia4 |
Increased
Description: Heterozygous females showed forepaw ataxia, measured by the ataxia coefficient (p=0.038)
Exp Paradigm: Measurement of ataxia coefficient: maximum stride length minus minimum stride length.
|
General observations |
4 months |
| |
|
Description: Heterozygous females showed forepaw ataxia, measured by the ataxia coefficient (p=0.038)
Exp Paradigm: Measurement of ataxia coefficient: maximum stride length minus minimum stride length. |
|
|
| Motor phenotype |
Motor coordination and balance4 |
Decreased
Description: Heterozygous females showed significant declines in motor coordination starting at 6 weeks, measured by a decreased latency to fall from rotarod during a progressively increasing rate of rotation.
Exp Paradigm: Measurement of latency to fall.
|
Accelerating rotarod test |
6-22 weeks |
| |
|
Description: Heterozygous females showed significant declines in motor coordination starting at 6 weeks, measured by a decreased latency to fall from rotarod during a progressively increasing rate of rotation.
Exp Paradigm: Measurement of latency to fall. |
|
|
| Motor phenotype |
General locomotor activity3 |
Decreased
Description: Decreased distance travelled
Exp Paradigm: Open field test
|
Open field test |
Unreported |
| |
|
Description: Decreased distance travelled
Exp Paradigm: Open field test |
|
|
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Brain size2 |
Decreased
Description: The brains of Mecp2 -/+ rats weighed significantly less than that of wild-type littermate females beginning at P21.
Exp Paradigm: Measurement of tissue weight
|
Measurement of tissue weight |
2-12 weeks |
| |
|
Description: The brains of Mecp2 -/+ rats weighed significantly less than that of wild-type littermate females beginning at P21.
Exp Paradigm: Measurement of tissue weight |
|
|
| Neurophysiology |
Synaptic transmission: excitatory1 |
Decreased
Description: Decreased amplitude and increased time
Exp Paradigm: In vivo local field potential (LFP) recordings, females
|
In vivo local field potential (lfp) recordings |
Unreported |
| |
|
Description: Decreased amplitude and increased time
Exp Paradigm: In vivo local field potential (LFP) recordings, females |
|
|
| Sensory |
Sensory-evoked response: excitation: auditory stimulus1 |
Decreased
Description: Decreased discrimination of sounds
Exp Paradigm: Application of auditory stimuli, females
|
Application of auditory stimuli |
Unreported |
| |
|
Description: Decreased discrimination of sounds
Exp Paradigm: Application of auditory stimuli, females |
|
|
| Sensory |
Pain or nociception: thermal: cold4 |
Increased
Description: A general tendency toward higher sensitivity to noxious cold was observed at 4 and 6 weeks, and differences became prominent from 8 weeks through 22 weeks.
Exp Paradigm: Cold sensitivity was measured using a Cold Plate Analgesia Meter. The average temperature at which nociceptive behaviors were seen is reported as the withdrawal threshold.
|
Cold plate analgesia meter |
4-22 weeks |
| |
|
Description: A general tendency toward higher sensitivity to noxious cold was observed at 4 and 6 weeks, and differences became prominent from 8 weeks through 22 weeks.
Exp Paradigm: Cold sensitivity was measured using a Cold Plate Analgesia Meter. The average temperature at which nociceptive behaviors were seen is reported as the withdrawal threshold. |
|
|
| Sensory |
Pain or nociception: mechanical4 |
Increased
Description: Thresholds rose for wildtype rats at 8 weeks as part of typical developmental course, but heterozygote rats remained hypersensitive throughout the adult life through 22 weeks.
Exp Paradigm: Von Frey filament applied to hind foot paw to determine threshold of withdrawal response.
|
Von frey filament test |
2-5 months |
| |
|
Description: Thresholds rose for wildtype rats at 8 weeks as part of typical developmental course, but heterozygote rats remained hypersensitive throughout the adult life through 22 weeks.
Exp Paradigm: Von Frey filament applied to hind foot paw to determine threshold of withdrawal response. |
|
|
| Social behavior |
Juvenile play3 |
Decreased
Description: Decreased contact, pounce and wrestling behaviors
Exp Paradigm: Reciprocal social interaction test
|
Reciprocal social interaction test |
4 weeks |
| |
|
Description: Decreased contact, pounce and wrestling behaviors
Exp Paradigm: Reciprocal social interaction test |
|
|
| Social behavior |
Social approach3 |
Decreased
Description: Decreased preference for stimulus rat
Exp Paradigm: Three-chamber social approach test
|
Three-chamber social approach test |
4 weeks |
| |
|
Description: Decreased preference for stimulus rat
Exp Paradigm: Three-chamber social approach test |
|
|
| Physiological parameters |
Metabolic function4 |
Decreased
Description: Heterozygote rats showed consistently lower metabolic values, with a significanly lower respiratory quotient detected during the light phase of the diurnal cycle.
Exp Paradigm: Metabolic indices measured by calorimetry during light and dark phases over a 48-h test period in wildtype and heterozygous rats.
|
Energy homeostasis analysis |
4 months |
| |
|
Description: Heterozygote rats showed consistently lower metabolic values, with a significanly lower respiratory quotient detected during the light phase of the diurnal cycle.
Exp Paradigm: Metabolic indices measured by calorimetry during light and dark phases over a 48-h test period in wildtype and heterozygous rats. |
|
|
| Physiological parameters |
Satiety response4 |
Increased
Description: Heterozygote rats ate substantially less food compared to wildtype, both at night time and daytime.
|
Food intake measurements |
4 months |
| |
|
Description: Heterozygote rats ate substantially less food compared to wildtype, both at night time and daytime.
|
|
|
| Physiological parameters |
Homeostasis: adiposity4 |
Increased
Description: Total body fat was elevated approximately three-fold in the heterozygote rats relative to the wildtype rats.
|
Magnetic resonance imaging (mri) |
4 months |
| |
|
Description: Total body fat was elevated approximately three-fold in the heterozygote rats relative to the wildtype rats.
|
|
|
| Physiological parameters |
Satiety response4 |
Decreased
Description: Daytime drinking in heterozygote rats was similar to wildtype; however, they drank approximately twice as much water at night relative to wildtype rats.
|
Water intake measurements |
4 months |
| Physiological parameters |
Digestive system function: gastrointestinal motility: peristaltic reflexes4 |
Decreased
Description: In response to applied colorectal pressures from 20 to 80 mm Hg, the visceromotor response increased in both wildtype and heterozygote rats. However, the heterozygous animals showed reduced visceromotor response relative to wildtype rats at pressures from 40 to 80 mm Hg, consistent with visceral hyposensitivity.
Exp Paradigm: Electromyographic recordings of visceromotor response in abdominal muscles, as a result from colorectal distension.
|
Electromyogram (emg) |
4 months |
| |
|
Description: In response to applied colorectal pressures from 20 to 80 mm Hg, the visceromotor response increased in both wildtype and heterozygote rats. However, the heterozygous animals showed reduced visceromotor response relative to wildtype rats at pressures from 40 to 80 mm Hg, consistent with visceral hyposensitivity.
Exp Paradigm: Electromyographic recordings of visceromotor response in abdominal muscles, as a result from colorectal distension. |
|
|
| Physiological parameters |
Respiratory function2 |
Increased
Description: Aged Mecp2 -/+ females show an enhanced respiratory frequency in conjunction with reduced expiratory time.
Exp Paradigm: Whole body plethysmography
|
Whole body plethysmography |
18 months |
| |
|
Description: Aged Mecp2 -/+ females show an enhanced respiratory frequency in conjunction with reduced expiratory time.
Exp Paradigm: Whole body plethysmography |
|
|
| Developmental profile |
Size/growth2 |
Increased
Description: Mecp2 -/+ rats displayed a tendency for weight gain, becoming significantly heavier than WTs by P60-P90.
Exp Paradigm: Body weight measurement, females
|
Body weight measurement |
2-18 months |
| |
|
Description: Mecp2 -/+ rats displayed a tendency for weight gain, becoming significantly heavier than WTs by P60-P90.
Exp Paradigm: Body weight measurement, females |
|
|
| Developmental profile |
Size/growth4 |
Increased
Description: Beginning at eight weeks of age heterozygote rats were heavier than wildtype, and the difference increased with time throughout the 22 weeks of the study.
|
Body weight measurement |
2-5 months |
| |
|
Description: Beginning at eight weeks of age heterozygote rats were heavier than wildtype, and the difference increased with time throughout the 22 weeks of the study.
|
|
|
| Emotion |
Anxiety3 |
Decreased
Description: Increased time spent in open area
Exp Paradigm: Elevated zero maze test
|
Elevated zero maze test |
3 weeks |
| |
|
Description: Increased time spent in open area
Exp Paradigm: Elevated zero maze test |
|
|
| Learning & memory |
Cued or contextual fear conditioning: memory of context3 |
Increased
Description: Increased freezing response
Exp Paradigm: Fear conditioning test
|
Fear conditioning test |
5 weeks |
| |
|
Description: Increased freezing response
Exp Paradigm: Fear conditioning test |
|
|
| Molecular profile |
Targeted expression2 |
Decreased
Description: Reduced levels of MECP2 protein in heterozygous females
Exp Paradigm: Western blot from cortex and brain stem of P60-80 males, and cortex of 15-week old females
|
Western blot |
2-3 months, 15 months |
| |
|
Description: Reduced levels of MECP2 protein in heterozygous females
Exp Paradigm: Western blot from cortex and brain stem of P60-80 males, and cortex of 15-week old females |
|
|
| Molecular profile |
Targeted expression3 |
Decreased
Description: An approximate 50% reduction in MeCP2 levels in female rats lacking one copy of Mecp2.
Exp Paradigm: Western blot
|
Western blot |
Unreported |
| |
|
Description: An approximate 50% reduction in MeCP2 levels in female rats lacking one copy of Mecp2.
Exp Paradigm: Western blot |
|
|
| Circadian sleep/wake cycle |
Locomotor activity in diurnal cycle: dark phase4 |
No change |
Beam crossing |
4 months |
| Developmental profile |
Mortality/lethality2 |
No change |
Survival analysis |
0-12 weeks |
| Developmental profile |
Size/growth4 |
No change |
Body weight measurement |
4-6 weeks |
| Learning & memory |
Cued or contextual fear conditioning: memory of cue3 |
No change |
Fear conditioning test |
5 weeks |
| Motor phenotype |
Motor coordination and balance4 |
No change |
Accelerating rotarod test |
4 weeks |
| Repetitive behavior |
Stereotypy3 |
No change |
General observations |
6 weeks |
| Sensory |
Olfaction3 |
No change |
Olfactory discrimination test |
6 weeks |
| Sensory |
Pain or nociception: mechanical4 |
No change |
Von frey filament test |
4-6 weeks |
| Sensory |
Pain or nociception: thermal4 |
No change |
Paw withdrawal test |
4-22 weeks |
| Sensory |
Sensorimotor gating3 |
No change |
Prepulse inhibition |
5 weeks |
| Sensory |
Startle response: acoustic stimulus3 |
No change |
Acoustic startle reflex test |
5 weeks |
|
| Not Reported: |
Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior, |
