TABLE 1.
Knock-In Mouse Models of HD
| Line Name | Original Strain* | CAG Number and Genetic Insertion | Behavioral Phenotype | Cellular and Molecular Phenotype | Neuropathology† | References |
|---|---|---|---|---|---|---|
| HdhQ50 | 129Sv × CD1 | Chimeric HD/Hdh exon 1 with 48 CAGs | No (up to 6 m) | 14 m: increased Rrs1 mRNA | No abnormalities (until 6 m) | 8, 26, 61 |
| HdhQ92 | 129Sv × CD1 | Chimeric HD/Hdh exon 1 with 90 CAGs | No (up to 17 m) | 8.5 m: increased Rrs1 mRNA, 9 m: somatic instability. | 5 m: nuclear staining, 12 m: nuclear microaggregates and inclusions | 20, 26, 61 |
| HdhQ111 | 129Sv × CD1 | Chimeric HD/Hdh exon 1 with 109 CAGs | 24 m: gait deficits | 3 w: increased Rrs1 mRNA, 1.5–2.5 m: decreased cAMP levels, 5 m: decreased BDNF and phospho-CREB levels, somatic instability | 1.5–2.5 m: nuclear staining, 4.5–5 m: nuclear microaggregates, 12 m: intranuclear inclusions consistently, 17: neuropil aggregates, 24 m: gliosis | 17, 20, 26, 48, 61, 67 |
| Hdh71 | 129Sv × C57BL/6J | Chimeric HD/Hdh exon 1 with 71 CAGs | No (up to 1 y) | Not observed. | No aggreagetes (up to 22 m) | 14, 19, 60 |
| Hdh94 | 129Sv × C57BL/6J | Chimeric HD/Hdh exon 1 with 94 CAGs | 2 m: hyperactivity, 4 m: hypoactivity, 24 m: Gait deficits | ∼3 m: increased sensitivity to NMDA, 4 m: decreased enkephalin mRNA levels | 6 m: nuclear staining and microaggregates, consistently. 18 m: intranuclear inclusions | 14, 19, 60 |
| Hdh140 | 129Sv × C57BL/6J | Chimeric HD/Hdh exon 1 with 140 CAGs | 1 m: hyperactivity, 4 m: hypoactivity, 12 m: gait deficits | n.r. | 4 m: nuclear staining and aggregates and neuropil aggregates, consistently | 13 |
| Hdh6/72 Hdh 4/80 | Sv129 × C57BL/6J, Sv129 × FVB/N | 72 and 80 CAGs, respectively | ∼3 m: aggression, 4 m: rotarod deficits‡ | 9 m: somatic instability | 4 m: nuclear staining, 11 m: nuclear aggregates, >11 m: neuropil aggregates, 17–22 m: axonal degeneration 21–27 m: intranuclear inclusions | 9, 27, 35, 46, 47, 49 |
| Hdh(CAG)80 | 129/Ola × C57BL/6J | 80 CAGs | >10 m: gait deficits, | n.r. | Nuclear inclusion rarely observed (up to 22 m) | 18 |
| Hdh(CAG)150 | 129/Ola × C57BL/6J | 150 CAGs | 4–10 m: gait and rotarod deficits, clasping, hypoactivity | 4 m: somatic instability, 11 m: clapain levels increased | 7–8 m: nuclear staining 14 m: gliosis, nuclear aggregates and inclusion, neuropil aggregates axonal degeneration, degenerated cytoplasmic organels | 18, 34, 45, 47 |
HD = human huntingtin gene; Hdh = mouse huntingtin gene; m = months of age; w = weeks of age; y = year old; n.r. = not reported; CREB, cAMP-responsive element binding protein.
*
Numerous lines have been backcrossed to various genetic backgrounds.
†
No cell loss was detected in knock-in models.
‡
Examinated in Hdh6/72 knock-in mice only.