Mouse Disease Timelines

Timelines

Line #	Onset	Pronounced	Experiment	Mouse Model	Phenotype Classification	Sub phenotype Classification	Phenotype location	Phenotype Characteristic / Test	Notes
1	4.5 wks	10-13 wks	10: 11353291	R6/2	Pathological/morphological	aggregates	brain/hippocampus DG	NII	DG, dentate gyrus; NII neuronal intranuclear inclusion; onset not well documented; immunogold anti-ubiquitin ab
2	11 wks	n/d	5: 16127709	R6/2	behavior	motor	organism	grip strength, forelimb
3	3 wks	5-7 wks	17: 15505789	R6/2	E-phys changes	receptor/neurotransmitter responses	brain/striatum/medium-sized spiny neurons	Increased frequency of spontaneous GABAergic synaptic currents
4	n/d	11-15 wks	18: 15625098	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	reduced membrane capacitance
5	8-9 wks	9-13.5 wks	7: 10191337	R6/2	behavior	motor	organism	footprint test	Gait changes seen at 8.5 wks were similar to those seen at 13.5 wks.
6	7 wks	10-11 wks	23: 10575040	R6/2	behavior	cognitive	organism	two-choice swim tank, acquisition (visual learning)
7	8.6 wks	12.9 wks	5: 16127709	R6/2	Pathological/morphological	atrophy	brain	brain volume decrease, ventricular
8	8 wks	13-14 wks	24: 16111888	R6/2	behavior	motor	organism	grip strength
9	8.6 wks	12.9 wks	5: 16127709	R6/2	Pathological/morphological	atrophy	brain	brain volume decrease
10	12.9 wks	n/d	5: 16127709	R6/2	Pathological/morphological	neurodegeneration	brain/striatum	decrease in striatal neuronal area/number
11	6 wks	12 wks	15: 10196370	R6/2	Pathological/morphological	atrophy	heart	atrophy
12	10.7-12.1 wks	n/d	16: 11746372	R6/2	E-phys changes	calcium channels	brain/striatum/medium-sized spiny neurons	reduced calcium current amplitude	neurons from pre-symptomatic mice (5-6.5 wks) had slightly higher peak calcium currents
13	n/d	10 wks	10: 11353291	R6/2	Pathological/morphological	aggregates	brain/thalamus	ENNI	ENNI, extranuclear inclusion; immunogold anti-ubiquitin ab
14	8-12 wks	n/d	1: 15579164	R6/2	E-phys changes	Non-CNS changes	neuromuscular junction	increased mconotoxin resistance
15	6 wks	8 wks	15: 10196370	R6/2	Pathological/morphological	aggregates	kidney	nuclear inclusions
16	4 wks	6-12 wks	6: 10369868	R6/2	Pathological/morphological	aggregates	brain/cortex	NII	NII, neuronal intranuclear inclusion; EM48 ab
17	6 wks	n/d	5: 16127709	R6/2	behavior	motor	organism	hindlimb clasping (dyskinesia)
18	8.6 wks	n/d	21: 10533044	R6/2	E-phys changes	receptor/neurotransmitter responses	brain/striatum/medium-sized spiny neurons	cell swelling in response to NMDA	also observed depolarized RMP, but did not discuss age of onset
19	n/d	7-13 wks	10: 11353291	R6/2	Pathological/morphological	aggregates	brain/hippocampus CA3	ENNI	ENNI, extranuclear inclusion; immunogold anti-ubiquitin ab
20	4 wks	6-12 wks	6: 10369868	R6/2	Pathological/morphological	aggregates	brain/striatum	NII	NII, neuronal intranuclear inclusion; EM48 ab
21	7 wks	8.5-12.5 wks	8: 10078572	R6/2	Pathological/morphological	metabolic	organism	diabetes
22	5-7 wks	11-15 wks	19: 12574425	R6/2	E-phys changes	action potential properties	brain/striatum/medium-sized spiny neurons	reduction in the frequency of spontaneous EPSC's	EPSP, excitatory postsynaptic potential
23	n/d	6 wks	22: 10829080	R6/2	E-phys changes	receptor/neurotransmitter responses	brain/striatum/medium-sized spiny neurons	reduced dopaminergic modulation of GABAA current	Lack of dopaminergic channel modulation was due to defects in the D1/cAMP/PKA/DARPP-32 signaling cascade.
24	8 wks	12-13 wks	7: 10191337	R6/2	behavior	motor	organism	excessive grooming/ hyperactivity
25	5-7 wks	9-14 wks	17: 15505789	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	increased input resistance	The change at 5-7 wks was observed, but not shown to be significant
26	n/d	7- 13 wks	10: 11353291	R6/2	Pathological/morphological	aggregates	brain/hippocampus CA1	ENNI	ENNI, extranuclear inclusion; immunogold anti-ubiquitin ab
27	39 wks	52 wks	26: 12812983	YAC 128	Pathological/morphological	atrophy	brain	brain weight loss	5% decrease in brain wt. at 9 mo, progressing to 10% at 12 mo.
28	n/d	12-13 wks	7: 10191337	R6/2	behavior	motor	organism	abrupt shuddering moments
29	8 wks	12 wks	15: 10196370	R6/2	Pathological/morphological	atrophy	liver	atrophy
30	4.3 wks	12.9 wks	5: 16127709	R6/2	Pathological/morphological	atrophy	brain	brain weight loss
31	8 wks	n/d	25: 16137562	R6/2	behavior	motor	organism	decreased anxiety (light/dark box)	Decreased anxiety was observed for both male and female mice, and may be a function of reduced activity at 8 wks.
32	5-6 wks	10+ wks	20: 10864968	R6/2	E-phys changes	synaptic plasticity	brain/hippocampus	CA1 / reduced LTP	LTP, long-term potentiation
33	6 wks	8 wks	15: 10196370	R6/2	Pathological/morphological	aggregates	pancreas	nuclear inclusions
34	11-15 wks	n/d	18: 15625098	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	decreased membrane time constants	time constants were slightly shorter, but not significantly shorter than wt
35	8 wks	n/d	23: 10575040	R6/2	behavior	cognitive	organism	visual cliff avoidance (visual learning)
36	11.6-14.4 wks	n/d	13: 11731527	R6/2	E-phys changes	action potential properties	brain/striatum/medium-sized spiny neurons	decreased AP decay slopes
37	n/d	11-15 wks	18: 15625098	R6/2	E-phys changes	potassium channels	brain/striatum/medium-sized spiny neurons	reduced inward potassium current density
38	6 wks	8 wks	15: 10196370	R6/2	Pathological/morphological	aggregates	adrenal glands	nuclear inclusions
39	11.6-14.4 wks	n/d	13: 11731527	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	depolarized RMPs	RMP, resting membrane potentials
40	n/d	39 wks	26: 12812983	YAC 128	Pathological/morphological	atrophy	brain/striatum	striatal volume	A 15% decrease in striatal volume was observed at 9 mo. No decrease detected at 6 mo.
41	4-9 wks	14 wks	24: 16111888	R6/2	behavior	motor	organism	decreased exploratory activity	Activity, mobility, and rearing were measured using the AM1053 activity cage system
42	10 wks	13 wks	2: 8898202	R6/2	Pathological/morphological	general	organism	survival	A single mouse, with symptom onset at 4.5 wks died early at 6.5 wks
43	12.9 wks	n/d	5: 16127709	R6/2	Pathological/morphological	atrophy	brain	brain volume decrease, striatal
44	9-11 wks	n/d	2: 8898202	R6/2	behavior	motor	organism	hindlimb clasping (dyskinesia)
45	5-6 wks	10+ wks	20: 10864968	R6/2	E-phys changes	synaptic plasticity	brain/hippocampus	CA1 / increased LTD	LTD, long-term depression
46	26 wks	52 wks	26: 12812983	YAC 128	behavior	motor	organism	decreased open field activity (dancenight)
47	4 wks	8 wks	25: 16137562	R6/2	behavior	motor	organism	decreased rearing activity
48	4 wks	n/d	9: 9267033	R6/2	Pathological/morphological	atrophy	brain	brain weight loss
49	11-15 wks	n/d	5: 16127709	R6/2	behavior	motor	organism	sustained flexure of forelimbs and hindlimbs
50	10.7-12.1 wks	n/d	16: 11746372	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	reduced membrane capacitance
51	13 wks	13 wks	26: 12812983	YAC 128	behavior	motor	organism	increased movements
52	12 wks	15 wks	1: 15579164	R6/2	Pathological/morphological	aggregates	skeletal muscle	nuclear inclusions
53	day 1	12.9 wks	5: 16127709	R6/2	Pathological/morphological	aggregates	brain/cortex	htt-positive aggregates
54	52 wks	n/d	26: 12812983	YAC 128	Pathological/morphological	atrophy	brain/cortex	cortex volume
55	8 wks	n/d	25: 16137562	R6/2	behavior	motor	organism	rotorod
56	8.5 wks	n/d	23: 10575040	R6/2	behavior	cognitive	organism	two-choice swim tank, retention (visual learning)
57	4.5 -5.5 wks	8.5- 9.5 wks	25: 16137562	R6/2	behavior	motor	organism	decreased running wheel activity (night)
58	5-6 wks	13-14 wks	7: 10191337	R6/2	behavior	motor	organism	rotorod
59	3-4 wks	5-7 wks	19: 12574425	R6/2	E-phys changes	action potential properties	brain/striatum/medium-sized spiny neurons	large-amplitude events
60	4 wks	12 wks	6: 10369868	R6/2	Pathological/morphological	aggregates	brain/cortex	ENNI	ENNI, extranuclear inclusion; EM48 ab
61	12-16 wks	n/d	1: 15579164	R6/2	E-phys changes	Non-CNS changes	neuromuscular junction	increased EPP failure	EPP, end-plate potential
62	7 wks	n/d	25: 16137562	R6/2	behavior	motor	organism	grip strength
63	12 wks	15 wks	1: 15579164	R6/2	Pathological/morphological	atrophy	skeletal muscle	atrophy
64	5-7 wks	11 wks	3: 16087879	R6/2	Pathological/morphological	atrophy	organism	weight loss
65	n/d	7 wks	20: 10864968	R6/2	behavior	cognitive	organism	Morris Water Maze (spatial learning)
66	n/d	13 wks	10: 11353291	R6/2	Pathological/morphological	aggregates	brain/striatum	ENNI	ENNI, extranuclear inclusion, most pronounced in large interneurons
67	10.7-12.1 wks	n/d	14: 11746372	R6/2	Pathological/morphological	neurodegeneration	brain/striatum	medium-sized spiny neurons/smaller somata
68	8-9 wks	13-14 wks	7: 10191337	R6/2	behavior	motor	organism	beam walking
69	8.6 wks	13.9 wks	5: 16127709	R6/2	Pathological/morphological	general	organism	survival	Less than 2% of the mice died prematurely through cfonstant seizure activity as early as 8.6 wks.
70	n/d	10 wks	10: 11353291	R6/2	Pathological/morphological	aggregates	brain/hippocampus DG	ENNI	ENNI, extranuclear inclusion; also seen in lacunosum moleculare; immunogold anti ubiquitin ab
71	3.5 wks	6-9 wks	11: 12115678	R6/2	Pathological/morphological	aggregates	brain/cortex	NII	NII, neuronal intranuclear inclusion; anti-ubiquitin ab, four mouse monoclonal abs, and polyclonal EM48 were used.
72	5.3-6.0 wks	11.6-14.4 wks	13: 11731527	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	increased input resistance
73	10 wks	13 wks	7: 10191337	R6/2	Pathological/morphological	atrophy	organism	weight loss
74	n/d	7- 10 wks	10: 11353291	R6/2	Pathological/morphological	aggregates	brain/thalamus	NII	NII, neuronal intranuclear inclusion; onset not well documented, immunogold anti-ubiquitin ab
75	11.6-14.4 wks	n/d	13: 11731527	R6/2	E-phys changes	action potential properties	brain/striatum	increased stimulation required to induce EPSPs	EPSP, excitatory postsynaptic potential
76	5-6 wks	10-13 wks	7: 10191337	R6/2	behavior	motor	organism	swimming tank (straight line)
77	3.5 wks	n/d	23: 10575040	R6/2	behavior	cognitive	organism	Morris Water Maze (spatial learning)
78	11.6-14.4 wks	n/d	13: 11731527	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	decreased membrane time constants
79	10.7-12.1 wks	n/d	16: 11746372	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	decreased membrane time constants
80	3 wks	6-8 wks	4: 16034568	R6/2	Pathological/morphological	aggregates	pancreas	beta cells/ubiquitin-positive inclusions
81	4 wks	12 wks	5: 16127709	R6/2	behavior	motor	organism	prolonged helicoptering of hindlimbs
82	n/d	12-13 wks	7: 10191337	R6/2	behavior	motor	organism	epileptic seizures
83	n/d	6 wks	22: 10829080	R6/2	E-phys changes	receptor/neurotransmitter responses	brain/striatum/medium-sized spiny neurons	reduced dopaminergic modulation of voltage-gated calcium current	Lack of dopaminergic channel modulation was due to defects in the D1/cAMP/PKA/DARPP-32 signaling cascade.
84	6.5 wks	8.5-11.5 wks	23: 10575040	R6/2	behavior	cognitive	organism	two-choice swim tank (reversal learning)
85	9.9 wks	n/d	5: 16127709	R6/2	Pathological/morphological	atrophy	organism	weight loss, female	Age specified represents onset of significant weight loss.
86	9-11 wks	n/d	2: 8898202	R6/2	behavior	motor	organism	tremor
87	52 wks	78 wks	26: 12812983	YAC 128	Pathological/morphological	aggregates	brain/striatum	htt-positive aggregates	Nuclear htt staining (antibody EM48) seen as "microaggregates" at 12 mo. Nuclear inclusions seen at 18 mo.
88	5-7 wks	n/d	19: 12574425	R6/2	E-phys changes	receptor/neurotransmitter responses	brain/striatum/medium-sized spiny neurons	Glu synaptic activity changes
89	6 wks	12 wks	15: 10196370	R6/2	Pathological/morphological	atrophy	skeletal muscle	atrophy	quadriceps and soleus muscle
90	10 wks	n/d	5: 16127709	R6/2	behavior	motor	organism	increased movements
91	n/d	11-15 wks	18: 15625098	R6/2	E-phys changes	potassium channels	brain/striatum/medium-sized spiny neurons	reduced outward potassium current density
92	11.6-14.4 wks	n/d	13: 11731527	R6/2	E-phys changes	action potential properties	brain/striatum/medium-sized spiny neurons	alterations in the ability to generate trains of APs
93	4 wks	n/d	25: 16137562	R6/2	behavior	motor	organism	decreased climbing activity
94	8 wks	8 wks	24: 16111888	R6/2	behavior	motor	organism	rotorod	Some drop off in rotorod performance seen at 4 wks
95	6 wks	12 wks	15: 10196370	R6/2	Pathological/morphological	aggregates	skeletal muscle	nuclear inclusions
96	day 1	12 .9 wks	5: 16127709	R6/2	Pathological/morphological	aggregates	brain/striatum	htt-positive aggregates
97	5.0-6.5 wks	10.7-12.1 wks	16: 11746372	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	increased input resistance
98	8-12 wks	8-12 wks	1: 15579164	R6/2	E-phys changes	Non-CNS changes	neuromuscular junction	increased EPP decay time	EPP, end-plate potential
99	9 wks	14 wks	4: 16034568	R6/2	Pathological/morphological	metabolic	organism	diabetes	Earliest onset of glucosuria was 9.3 wks. Glucose intolerance was detected at 9 wks. Aggressive behavioral testing (swimming) accelerated the onset of diabetes.
100	6.4 wks	12 wks	5: 16127709	R6/2	Pathological/morphological	neurodegeneration	brain/striatum	progressive neurodegeneration
101	12 + wks	15 wks	1: 15579164	R6/2	Pathological/morphological	neurodegeneration	neuromuscular junction	AChR defects	onset not well documented
102	6 wks	12 wks	15: 10196370	R6/2	Pathological/morphological	atrophy	kidney	atrophy
103	12.9 wks	n/d	5: 16127709	R6/2	Pathological/morphological	neurodegeneration	brain/striatum	increased reactive astrogliosis
104	5-7 wks	11-15 wks	18: 15625098	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	increased input resistance
105	3 wks	10 wks	10: 11353291	R6/2	Pathological/morphological	aggregates	brain/cortex	NII	NII, neuronal intranuclear inclusion; onset not well documented, immunogold anti-ubiquitin ab
106	4 wks	8 wks	15: 10196370	R6/2	Pathological/morphological	atrophy	testes	atrophy
107	5-7 wks	9-14 wks	17: 15505789	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	reduced membrane capacitance	The change at 5-7 wks was observed, but not shown to be significant
108	n/d	11-15 wks	18: 15625098	R6/2	E-phys changes	basic membrane properties	brain/striatum/medium-sized spiny neurons	depolarized RMPs
109	16 wks	20 wks	1: 15579164	R6/2	Pathological/morphological	general	organism	survival
110	4.5-5.5 wks	n/d	25: 16137562	R6/2	behavior	motor	organism	increased anxiety (light/dark box)	Anxiety was only observed in male R6/2 mice at 4.5-5.5 wks.
111	5-6.5 wks	10.7-12.1 wks	16: 11746372	R6/2	E-phys changes	receptor/neurotransmitter responses	brain/striatum/medium-sized spiny neurons	increased NMDA response	NMDA-induced peak currents and current densities were higher for in a "responsive" subpopulation of R6/2 mice neurons vs WT mouse neurons
112	8 wks	12-13 wks	7: 10191337	R6/2	behavior	motor	organism	irregular gait
113	n/d	52 wks	26: 12812983	YAC 128	Pathological/morphological	neurodegeneration	brain/striatum	striatal neurons/ smaller somata	18% decrease in neuronal area.
114	52 wks	78 wks	26: 12812983	YAC 128	Pathological/morphological	aggregates