Species: Mouse
Genes: LRRK2
Mutations: LRRK2 R1441C
Modification: LRRK2: Transgenic
Disease Relevance: Parkinson's Disease
Strain Name: STOCK Gt(ROSA)26Sortm1(LRRK2*R1441C)Djmo/J
Summary
R26-LRRK2+/+ mice harbor a transgene containing a full-length mutant human LRRK2 preceded by a floxed stop cassette, inserted into the ROSA26 locus; these mice allow for conditional expression of human LRRK2 R1441C when crossed with mice carrying a transgene for Cre recombinase.
Phenotype Characterization
When visualized, these models will distributed over a 18 month
timeline
demarcated at the following intervals: 1mo, 3mo, 6mo,
9mo, 12mo, 15mo, 18mo+.
Neuronal Loss
In the substantia nigra pars compacta, there was no difference in the number of TH-positive neurons or the total number of Nissl-positive neurons at 12 and 22 months.
Dopamine Deficiency
HPLC analysis of striata from 10-month-old mice revealed no significant differences in the levels of dopamine or its metabolites DOPAC and HVA.
α-synuclein Inclusions
Immunohistochemical analysis of the brain at 22 months did not reveal abnormalities in α-synuclein, and no proteinaceous inclusions were seen.
Neuroinflammation
Immunohistochemical analysis of the brain at 22 months found GFAP and Iba1 immunoreactivity comparable to control levels.
Mitochondrial Abnormalities
Motor Impairment
Around 20 months of age, R26-LRRK2 mice behaved normally, exhibiting no deficits in locomotor activity (open-field test), motor coordination (Rotarod), or gait (digital CatWalk system).
Non-Motor Impairment
Olfactory function, as assessed by the ability to locate buried food, was normal out to 20 months of age.
Last Updated: 03 May 2024
Further Reading
No Available Further Reading
Species: Rat
Genes: Lrrk2
Modification: Lrrk2: Knock-Out
Disease Relevance: Parkinson's Disease
Strain Name: LEH-Lrrk2tm1sage, HsdSage: LE-Lrrktm1sage, formerly known as TGRL4620
Summary
Phenotype Characterization
When visualized, these models will distributed over a 18 month
timeline
demarcated at the following intervals: 1mo, 3mo, 6mo,
9mo, 12mo, 15mo, 18mo+.
Neuronal Loss
Under basal conditions, the number of TH-positive cells in the substantia nigra is comparable between Lrrk2 KO and wild-type rats. When challenged with LPS or α-synuclein overexpression, Lrrk2 KO rats develop significantly less neurodegeneration in the substantia nigra than wild-type rats.
Dopamine Deficiency
Basal levels of dopamine metabolites (3,4-dihydroxyphenylacetic and homovanillic acid) do not differ between Lrrk2 KO and wild-type rats at 4, 8, and 12 months of age. Evoked release of dopamine also does not differ between KO and wild-type rats.
Neuroinflammation
When challenged with LPS or α-synuclein overexpression, Lrrk2 KO rats show lower levels of pro-inflammatory CD68-positive myeloid cells in the substantia nigra than wild-type rats.
Mitochondrial Abnormalities
Motor Impairment
Assessment of Rotarod performance revealed no impairment at 12 months of age compared with wild-type rats.
Non-Motor Impairment
Abnormalities occur in peripheral organs, most notably the kidney, but also the liver, lung, and spleen. Changes are progressive, although they do not appear to shorten lifespan. The earliest reported alterations occur in the kidneys at 1 month of age.
Last Updated: 19 Sep 2023
Further Reading
No Available Further Reading
Species: Rat
Genes: Park2
Modification: Park2: Knock-Out
Disease Relevance: Parkinson's Disease
Strain Name: HsdSage:LE-Park2em1Sage; formerly LEH-Park2TM1sage
Summary
Phenotype Characterization
When visualized, these models will distributed over a 18 month
timeline
demarcated at the following intervals: 1mo, 3mo, 6mo,
9mo, 12mo, 15mo, 18mo+.
Neuronal Loss
A small, non-significant reduction in dopaminergic neurons was observed in the substantia nigra at 8 months of age.
Dopamine Deficiency
No differences in striatal dopamine levels at 4, 6, or 8 months. Altered dopaminergic transmission factors in the striata, including MAO, β-phenylethylamine, trace amine-associated receptor 1, and postsynaptic dopamine D2 receptors in 2-month-old KO rats. Striatal dopamine metabolite levels decreased with age in KO rats, showing lower levels at 12 months than at 8 months.
α-synuclein Inclusions
There was no increase in α-synuclein protein in the striatum or any other brain region assessed.
Mitochondrial Abnormalities
Alterations in mitochondrial protein expression in synaptic and nonsynaptic striatal samples of 3-month-old KO rats.
Motor Impairment
No behavioral deficits were detected at 4, 6, and 8 months of age. Motor functioning, including performance on the Rotarod, was intact. However, at 2 months, male KO rats made fewer small stereotypic movements, such as scratching and grooming, than wild-type controls.
Non-Motor Impairment
Orientation to an olfactory stimulus was normal. At 2 months of age, male KO rats had a greater preference for methamphetamine than wild-type rats based on self-administration and place preference tests.
Last Updated: 11 Oct 2023
Further Reading
No Available Further Reading
Species: Rat
Genes: Pink1
Modification: Pink1: Knock-Out
Disease Relevance: Parkinson's Disease
Strain Name: HsdSage:LE-Pink1em1Sage; formerly LEH-Pink1tm1Sage-/-
Summary
Phenotype Characterization
When visualized, these models will distributed over a 18 month
timeline
demarcated at the following intervals: 1mo, 3mo, 6mo,
9mo, 12mo, 15mo, 18mo+.
Neuronal Loss
Age-related decrease in tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra. A reduction of 25 and 50 percent at 6 months and 8 months, respectively. Deficits in TH staining in the substantia nigra have been observed as early as at 2.5 months of age. While some studies did not see any changes in TH-positive cells in the striatum, others have observed a 15% loss.
Dopamine Deficiency
One study found striatal dopamine levels were increased two- to threefold in Pink1 KO rats compared with wild-type levels at 8 months of age, whereas another reported a slight decrease at this age. In the dorsal striatum, KO rats have age-dependent differences in basal and evoked dopamine levels, but no differences were observed compared to wild-type rats.
α-synuclein Inclusions
Alpha-synuclein aggregates were found as early as 4 months of age and increased in number up to 12 months. Areas affected include the periaqueductal gray, substantia nigra pars compacta, locus coeruleus, nucleus ambiguous, cortex, thalamus, and striatum.
Mitochondrial Abnormalities
Alterations in mitochondrial metabolites and mitochondrial protein expression were reported as early as 4 months of age in cortex and striatum. Oxygen consumption rates were elevated in striatal mitochondria isolated from 9-month-old rats, but not in non-synaptic samples from 3-month-old rats.
Motor Impairment
Abnormalities in gait, coordination, and strength. By 5 weeks, KOs had increased foot slips on the tapered balance beam, at 7 weeks they showed hind limb fatigue, which progressed to hind limb dragging, and by 2 months they exhibited alterations in oromotor behaviors. Deficits in gait may be transient. Partial reversal of motor impairment by Levodopa.
Non-Motor Impairment
Nociception alterations in male KO rats observed at 6 to 10 months of age, indicating thermal hyperalgesia. This effect was present in female KO rats at 2 months of age, but not at older ages. Abnormalities in ventilation frequency were also observed in male KO rats. Defects in ultrasonic vocalizations starting at 2 months of age in male and female KO rats.
Last Updated: 06 Apr 2024
Further Reading
No Available Further Reading
Species: Mouse
Genes: SNCA
Mutations: SNCA A30P, SNCA A53T
Modification: SNCA: Transgenic
Disease Relevance: Parkinson's Disease
Strain Name: C57BL/6J-Tg(Th-SNCA*A30P*A53T)39Eric/J
Summary
This transgenic mouse model of Parkinson’s disease, called the HM2 model, expresses mutant human α-synuclein in dopaminergic neurons. Hemizygous mice exhibit age-related abnormalities in the dopaminergic system, including low dopamine levels and difficulties with motor coordination (Richfield et al., 2002).
Phenotype Characterization
When visualized, these models will distributed over a 18 month
timeline
demarcated at the following intervals: 1mo, 3mo, 6mo,
9mo, 12mo, 15mo, 18mo+.
Neuronal Loss
Progressive loss of dopaminergic neurons was reported in the substantia nigra pars compacta (19 percent reduction at 8.5 months and 55 percent at 19 months).
Dopamine Deficiency
Striatal dopamine concentrations were lower at all ages tested, including the earliest age, 2-3 months. Dopamine concentrations dropped with age, and levels of metabolites (e.g., DOPAC and HVA) were also lower in HM2 mice than non-Tg by 13-23 months of age.
α-synuclein Inclusions
Inclusions were not observed at any age. Diffuse α- synuclein protein was both cytoplasmic and nuclear.
Mitochondrial Abnormalities
Motor Impairment
At young age 2-3 months, HM2 mice were more active than non-Tg controls, but by middle age (7-9 months) they were less active. At advanced ages (13-23 months), they also exhibited impaired coordination as measured by the time it took to right themselves from an inverted wire screen. However, no deficiencies in Rotarod performance, grip strength, or open-field movements were detected at 6 months.
Last Updated: 07 Feb 2019
Further Reading
No Available Further Reading
Species: Mouse
Genes: SNCA, SNCA
Mutations: SNCA A53T
Modification: SNCA: Transgenic; SNCA: Knock-Out
Disease Relevance: Parkinson's Disease
Strain Name: FVB;129S6-Sncatm1Nbm Tg(SNCA*A53T)1Nbm Tg(SNCA*A53T)2Nbm/J
Summary
Phenotype Characterization
When visualized, these models will distributed over a 18 month
timeline
demarcated at the following intervals: 1mo, 3mo, 6mo,
9mo, 12mo, 15mo, 18mo+.
Neuronal Loss
No evidence of neuronal cell loss in the substantia nigra at 11 and 18 months of age, including dopaminergic neurons (TH-positive neurons) and total neurons.
Dopamine Deficiency
No differences in striatal dopamine concentrations, or dopaminergic metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) at 11 and 18 months of age.
α-synuclein Inclusions
No evidence of Lewy body-like inclusions in the brain at any age. Likewise α-synuclein aggregates were not observed in the brain, although they did occur in enteric neurons in the gut.
Mitochondrial Abnormalities
Motor Impairment
By 6 months of age, homozygous mice became hypoactive, traveling less distance. This was not attributed to changes in exploratory behavior caused by anxiety. Also at 6 months, differences in performance on the accelerating Rotarod were seen.
Non-Motor Impairment
By 3 months of age, the mice develop gastrointestinal dysfunction.
Last Updated: 22 Mar 2017
Further Reading
No Available Further Reading
Species: Mouse
Genes: SNCA
Modification: SNCA: Knock-Out
Disease Relevance: Parkinson's Disease
Strain Name: N/A
Summary
Phenotype Characterization
When visualized, these models will distributed over a 18 month
timeline
demarcated at the following intervals: 1mo, 3mo, 6mo,
9mo, 12mo, 15mo, 18mo+.
Neuronal Loss
No gross abnormalities in the brain.
Dopamine Deficiency
A possible modest reduction in striatal dopamine level, but highly variable from mouse to mouse.
Neuroinflammation
Microglia cultured from Snca KO brain were more reactive, ramified. They had vacuole-like structures. Snca KO microglia exhibited exacerbated response to LPS, with greater secretion of pro-inflammatory cytokines.
Mitochondrial Abnormalities
Mitochondrial abnormalities include reduced levels of the mitochondrial phospholipid cardiolipin and reduced activity of electron transport chain complex I/III.
Motor Impairment
Motor function was largely intact. Normal performance on the Rotarod and in total distance travelled in the open field test. Subtle differences only (e.g., less rearing behavior than controls). They also spent less time in the center of the field, suggesting a possible anxiety-related phenotype.
Non-Motor Impairment
The mice had normal reflexes and sensory abilities. Also, learning and memory appeared intact at 6-10 months of age, as assesed by the Morris water maze and tests of conditioned fear memory.
Last Updated: 22 Mar 2017
Further Reading
No Available Further Reading
Species: Mouse
Genes: SNCA
Modification: SNCA: Conditional Knock-out
Disease Relevance: Parkinson's Disease
Strain Name: B6(Cg)-Sncatm1.1Vlb/J
Summary
Breeding these mice with various Cre-expressing transgenic mice allows for the depletion of α-synuclein in specific cell populations (Ninkina et al., 2015).
Phenotype Characterization
When visualized, these models will distributed over a 18 month
timeline
demarcated at the following intervals: 1mo, 3mo, 6mo,
9mo, 12mo, 15mo, 18mo+.
Mitochondrial Abnormalities
Last Updated: 24 Dec 2024
Further Reading
No Available Further Reading
Species: Rat
Genes: LRRK2
Mutations: LRRK2 G2019S
Modification: LRRK2: Transgenic
Disease Relevance: Parkinson's Disease
Strain Name: NTac:SD-Tg(LRRK2*G2019S)571CJLi
Summary
This transgenic (Tg) rat model overexpresses mutant Lrrk2. It was originally developed in the laboratory of Chenjian Li and then re-derived at Taconic with the support of the Michael J. Fox Foundation.
Phenotype Characterization
When visualized, these models will distributed over a 18 month
timeline
demarcated at the following intervals: 1mo, 3mo, 6mo,
9mo, 12mo, 15mo, 18mo+.
Neuronal Loss
No overt loss of dopaminergic neurons in the substantia nigra out to 12 months of age.
Dopamine Deficiency
No change in striatal dopamine levels. No change in 3,4-dihydroxyphenylacetic acid (DOPAC) levels. No change in the rate of dopamine turnover. At 12 months of age Tg rats exhibited higher levels of striatal homovanillic acid (HVA).
α-synuclein Inclusions
Under basal conditions no α-synuclein inclusions were observed.
Neuroinflammation
No increase in Iba-1 positive microglia or GFAP-positive astrocytes in the substantia nigra at 12 months of age. However, iNOS expression was elevated in nigral dopaminergic neurons.
Mitochondrial Abnormalities
Motor Impairment
Mild abnormalities in motor behavior. Slightly more postural instability at 8 months of age (but not at 4 and 12 months). Slightly more rearing events at 12 months, but not at younger ages.
Non-Motor Impairment
Bone marrow myeloid progenitor numbers were decreased, but suppressive myeloid cells were increased at 6 to 11 months of age
Last Updated: 18 Jan 2024
Further Reading
No Available Further Reading
Species: Mouse
Genes: SNCA
Mutations: SNCA A53T
Modification: SNCA: Transgenic
Disease Relevance: Parkinson's Disease
Strain Name: B6.Cg-2310039L15RikTg(Prnp-SNCA*A53T)23Mkle/J. Formerly: B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J
Summary
These transgenic mice overexpress human α-synuclein with a PD-associated mutation (A53T). Hemizygous mice overexpress mutant α-synuclein in the brain at levels about sixfold higher than endogenous mouse α-synuclein. They develop severe progressive motor impairments around one year of age, but no overt neuronal loss (Lee et al., 2002). The data on this page refer to phenotypes observed in hemizygous animals; homozygous mice from this strain are not viable.
Phenotype Characterization
When visualized, these models will distributed over a 18 month
timeline
demarcated at the following intervals: 1mo, 3mo, 6mo,
9mo, 12mo, 15mo, 18mo+.
Neuronal Loss
Overt neuronal loss was not reported in these mice.
Dopamine Deficiency
In symptomatic mice, striatal dopamine and metabolites DOPAC and HVA are comparable to wildtype, but at 5 months, striatal tyrosine hydroxylase is reduced. Increased D1 receptors in the substantia nigra and decreased dopamine transporters in the nucleus accumbens and striatum have been reported.
α-synuclein Inclusions
Prior to motor deficits, these mice develop accumulations of α-synuclein in select neuronal populations, including the midbrain, cerebellum, brainstem, and spinal cord. The protein aggregates do not resemble Lewy bodies, but are thioflavin-S-positive, indicating fibrillar structure.
Neuroinflammation
In symptomatic mice, increased GFAP immunoreactivity was observed in select brain regions, including the dorsal midbrain, deep cerebellar nuclei, brainstem, and spinal cord. Cortex, hippocampus, and substantia nigra did not have increased reactivity compared with non-Tg controls.
Mitochondrial Abnormalities
At 11–14 months, mitochondria in brainstem neurons were enlarged and their co-localization with the mitochondrial fission protein Drp1 was reduced.
Motor Impairment
These mice develop severe motor impairment starting around 9-16 months of age. The deficits start out with mild hyperactivity at 7 months and progress to a wobbling movement, decreased activity, and ultimately paralysis and death.
Non-Motor Impairment
At 11–12 months, spatial memory was impaired as assessed by the Barnes circular maze.
Last Updated: 08 Feb 2019
Further Reading
No Available Further Reading
David Holtzman 
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