Table 2.
Summary of transgenic mouse lines used for the temporospatial manipulation of ASD genes in the mouse brain.
| Cre line (or “Tet-Off” line) | Commercial availability | Cells targeted | Timing of gene expression manipulation | Social communication phenotypes | Repetitive behavior phenotypes | References |
|---|---|---|---|---|---|---|
| CamKII-cre93 | EMMA 01137 | Excitatory forebrain neurons | Postnatal (~P21) |
Mecp2 (loxP/y)
↓ Sociability* ↓ Social novelty*** NR USVs NR nest-building |
Mecp2 (loxP/y)
NR grooming NR hole board NR marble-burying |
Cre line primary: [70] Mecp2 study: [29] |
| CamKIIα-cre T29-1 | JAX 005359 | Excitatory forebrain neurons | Postnatal (~P21) |
Cc2d1a (loxP/loxP) ↓ Sociability*, **** NR social novelty ↓ Adult USVs NR nest-building Tsc1 (loxP/loxP) ↓ Sociability* NR social novelty NR USVs NR nest-building |
Cc2d1a (loxP/loxP) ↑ Grooming NR hole board ↔ Marble-burying Tsc1 (loxP/loxP) NR grooming NR hole board ↑ Marble-burying |
Cre line primary: [20] Cc2d1a study: [33] Tsc1 study: [34] |
| Emx1-cre | JAX 005628 | Excitatory forebrain neurons and glia | Embryonic |
Mecp2 (loxP/y)
↔ Sociability* ↔ Social novelty* NR USVs NR nest-building Mef2c (loxP/loxP) ↓ Sociability* NR social novelty ↓ Pup, adult USVs ↓ Nest-building |
Mecp2 (loxP/y)
NR grooming NR hole board NR marble-burying Mef2c (loxP/loxP) NR grooming NR hole board NR marble-burying |
Cre line primary: [71] Mecp2 study: [30] Mef2c study: [32] |
| Vglut2-cre | JAX 028863 | All glutamatergic neurons | Embryonic |
Mecp2 (loxP/y)
↔ Sociability** NR social novelty NR USVs NR nest-building Mecp2 (loxP-stop/y) ↑ Sociability** resc. NR social novelty NR USVs NR nest-building |
Mecp2 (loxP/y)
NR grooming ↔ Hole board NR marble-burying Mecp2 (loxP-stop/y) NR grooming ↑ Hole board resc. NR marble-burying |
Cre line primary: [72] Mecp2 study: [31] |
| Viaat-cre | JAX 017535 | All GABAergic neurons | Embryonic |
Mecp2 (loxP/y)
↑ Sociability*, ** NR social novelty NR USVs ↓ Nest-building Mecp2 (loxP-stop/y) ↑ Sociability** resc. NR social novelty NR USVs ↓ Nest-building resc. |
Mecp2 (loxP/y)
↑ Grooming ↑ Hole board NR marble-burying Mecp2 (loxP-stop/y) NR grooming NR hole board NR marble-burying |
Cre line primary: [35] Mecp2 deletion study: [35] Mecp2 rescue study: [36] |
| Dlx5/6-cre | JAX 008199 | Subset of GABAergic neurons in forebrain | Embryonic |
Mecp2 (loxP/y)
↑ Sociability*, ** NR social novelty NR USVs ↓ Nest-building |
Mecp2 (loxP/y)
↔ Grooming ↑ Hole board NR marble-burying |
Cre line primary: [73] Mecp2 study: [35] |
| PV-cre | JAX 008069 | PV+ GABAergic neurons | Embryonic |
Mecp2 (loxP/y)
↑ Sociability** ↔ Sociability* NR social novelty NR USVs NR nest-building Scn1a (loxP/+) ↓ Sociability* NR social novelty NR USVs NR nest-building |
Mecp2 (loxP/y)
NR grooming ↔ Hole board NR marble-burying Scn1a (loxP/+) NR grooming NR hole board NR marble-burying |
Cre line primary: [74] Mecp2 studies: [38, 39] Scn1a study: [40] |
| SOM-cre | JAX 013044 | SOM+ GABAergic neurons | Embryonic |
Mecp2 (loxP/y)
↔ Sociability** NR social novelty NR USVs NR nest-building Scn1a (loxP/+) ↔ Sociability* NR social novelty NR USVs NR nest-building |
Mecp2 (loxP/y)
NR grooming ↑ Hole board NR marble-burying Scn1a (loxP/+) NR grooming NR hole board NR marble-burying |
Cre line primary: [75] Mecp2 study: [38] Scn1a study: [40] |
| PET-1 cre | JAX 012712 | All serotonergic neurons | Embryonic |
Mecp2 (loxP/y)
↑ Sociability** ↑ Aggression**** NR social novelty NR USVs NR nest-building |
Mecp2 (loxP/y)
↔ Grooming NR hole board ↔ Marble-burying |
Cre line primary: [76] Mecp2 study: [41] |
| Slc6a4-cre | MMRRC 031028-UCD | All serotonergic neurons | Embryonic |
Tsc1 (loxP/loxP)
↓ Sociability* NR social novelty NR USVs NR nest-building |
Tsc1 (loxP/loxP) NR grooming NR hole board ↑ Marble-burying |
Cre line primary: [77] Tsc1 study: [34] |
| TH-cre | EMMA 00254 | All dopaminergic neurons | Embryonic |
Mecp2 (loxP/y)
↔ Sociability** ↔ Aggression**** NR social novelty NR USVs NR nest-building |
Mecp2 (loxP/y)
NR grooming NR hole board NR marble-burying |
Cre line primary: [78] Mecp2 study: [41] |
| Chat-cre | JAX 006410 | All cholinergic neurons | Embryonic |
Mecp2 (loxP/y)
↓ Sociability**** ↓ Social novelty* NR USVs ↓ Nest-building |
Mecp2 (loxP/y)
NR grooming NR hole board NR marble-burying |
Cre line primary: [79] Mecp2 study: [45] |
| Oxt-cre | JAX 024234 | All oxytocinergic neurons | Embryonic |
Pten (loxP/+) and Pten (loxP/loxP)
↔ Sociability*, *** ↔ Social novelty*, *** NR USVs NR nest-building |
Pten (loxP/+) and Pten (loxP/loxP)
NR grooming NR hole board ↔ Marble-burying |
Cre line primary: [80] Pten study: [46] |
| L7-cre | JAX 004146 | Cerebellar Purkinje cells | Early postnatal |
Tsc1 (loxP/+) and Tsc1 (loxP/loxP) ↓ Sociability* ↓ Social novelty* NR USVs NR nest-building Tsc2 (loxP/-) ↓ Sociability* ↓ Social novelty* NR USVs NR nest-building Pten (loxP/loxP) ↓ Sociability* NR social novelty NR USVs NR nest-building Shank2e6-7 (loxP/loxP) ↓ Sociability* ↓ Social novelty* NR USVs NR nest-building |
Tsc1 (loxP/+) and Tsc1 (loxP/loxP) ↑ Grooming NR hole board NR marble-burying Tsc2 (loxP/-) NR grooming NR hole board ↑ Marble-burying Pten (loxP/loxP) ↓ Grooming NR hole board NR marble-burying Shank2e7 (loxP/loxP) ↔ Grooming NR hole board ↔ Marble-burying |
Cre line primary: [81] Tsc1 study: [52] Tsc2 study: [53] Pten study: [54] Shank2 study: [56] |
| Pcp2-cre | JAX 010536 | Cerebellar Purkinje cells | Early postnatal |
Shank2e7 (loxP/loxP)
↔ Sociability* ↔ Social novelty* ↔ Adult USVs NR nest-building |
Shank2e6-7 (loxP/loxP)
↔ Grooming ↑ Hole board ↔ Marble-burying |
Cre line primary: [82] Shank2 study: [57] |
| Gfap-cre | N/A | Mostly cerebellar granule cells, few hippocampal neurons | Unclear |
Pten (loxP/loxP)
↓ Sociability*, ** NR social novelty ↔ Pup USVs NR nest-building |
Pten (loxP/loxP)
NR grooming ↓ Hole board ↓ Marble-burying |
Cre line primary: [83] Pten study: [55] |
| CAGGS-CreER | JAX 004453 | Ubiquitous | Concurrent with tamoxifen administration (P60+ for all examples) |
Mecp2 (loxP/y) NR sociability NR social novelty NR USVs ↓ Nest-building Mecp2 (loxP-stop/y) and Mecp2 (loxP-stop/+) NR sociability NR social novelty NR USVs ↓ Nest-building resc. Ube3a (loxP-stop/p+) NR sociability NR social novelty NR USVs ↓ Nest-building no resc. Shank3 (loxP/loxP) inverted ↓ Sociability* resc. ↓ Social novelty* resc. NR USVs NR nest-building |
Mecp2 (loxP/y) NR grooming NR hole board NR marble-burying Mecp2 (loxP-stop/y) and Mecp2 (loxP-stop/+) NR grooming NR hole board NR marble-burying Ube3a (loxP-stop/p+) NR grooming NR hole board ↓ Marble-burying no resc. Shank3 (loxP/loxP) inverted ↑ Grooming resc. NR hole board NR marble-burying |
Cre line primary: [84] Mecp2 deletion study: [60] Mecp2 rescue study: [61] Ube3a study: [64] Shank3 study: [66] |
| CaMKII-tTA | JAX 003010 | Excitatory forebrain neurons | Concurrent with doxycycline administration (P60+ for this example) |
TRE-HAβnrx1ΔC
↓ Sociability* resc. ↓ Social novelty* resc. NR USVs NR nest-building |
TRE-HAβnrx1ΔC
↑ Grooming resc. NR hole board NR marble-burying |
Tet-Off line primary: [85] Nrxn1β study: [65] |
NR behavioral test not reported, resc. abnormal phenotype was rescued with genetic manipulation, no resc. genetic manipulation failed to rescue abnormal phenotype, JAX The Jackson Laboratory, EMMA The European Mouse Mutant Archive, MMRRC Mutant Mouse Resource & Research Centers.
* In the three chamber test; ** in the partition test; *** in the habituation/dishabituation test; **** in a direct social interaction test.
↑ Mutant mice have significantly elevated amounts of this behavior when compared to controls.
↓ Mutant mice have significantly decreased amounts of this behavior when compared to controls.
↔ There were no significant differences between mutants and their controls on this behavioral test.