These transgenic mice express the cholera toxin intracellular enzymatic subunit A1 under the direction of the human dopamine receptor D1, DRD1, promoter. Expression of the cholera toxin in the D1 dopamine receptor subtype neurons results in chronic potentiate neural activity in this specific neuron subset. This mutant mouse strain may be useful in studies of obsessive-compulsive disorder (OCD), Gilles De La Tourette Syndrome and Trichotillomania.
Frank H Burton, University of Minnesota
These transgenic mice express the cholera toxin intracellular enzymatic subunit A1 under the direction of the human dopamine receptor D1, DRD1, promoter. Expression of the cholera toxin in the D1 dopamine receptor subtype-expressing neurons results in chronic potentiation of neural activity in this specific neuron subset. CNS expression of the transgene is regionally restricted and is detected only in the piriform cortex layer II, the amygdalar intercalated nucleus (ICN), and the somatosensory cortical areas layer II-III. Transgenic mice have elevated cortical cAMP levels. Transgenic mice exhibit trichotillomania-like excessive grooming, plucking, scratching and non-aggressive biting behavior during self- and social-grooming, as early as 3 weeks of age. These behaviors can result in skin, tail or periorbital (eye area) lesions on the transgenic mice and to skin or tail lesions on their cagemates. Hyperlocomotion (increased motion, wall leaping, gnawing) that is similar to drug induced hyperactivity, other psychomotor abnormalities are also displayed by transgenic mice as well as obsessive-compulsive disorder-like episodes of generalized perseveration of all otherwise normal behaviors. Transgenic mice exhibit increased anxiety response, as measured by behavioral indicators such as increased thigmotaxis (tendency to remain along the perimeter walls of an open area), and Tourette's Syndrome-like behaviors (juvenile-onset tics in both transgenic males and females, with increased tic severity and flurries in transgenic males). Transgenic mice may appear slightly smaller than wildtype littermates and can develop a more hunched and scruffy appearance in adulthood. Homozygous and hemizygous mice have significant breeding difficulty, viability obstacles, and reduced transgene inheritance (see details below). This mutant mouse strain may be useful in studies of Gilles De La Tourette Syndrome, obsessive-compulsive disorder (OCD) and Trichotillomania.
Homozygous and hemizygous females do not breed and are not good mothers due to their anxiety and grooming-biting phenotype (leading to biting of litters). Homozygous and hemizygous males are fertile, but may sometimes bite their litters. Transgenic mice housed with cagemates may inadvertently but repeatedly injure them (e.g., tail loss, skin wounds) by excessively biting during social grooming; these injuries can be minimized by housing transgenic mice with multiple cagemates and including an interior domicile (mouse dome) in the cage as a retreat. When breeding wildtype or BALB/c females with transgenic males at The Jackson Laboratory Repository, pups exhibit diminished transgene inheritance (~33% rather than the expected ~50%).
A transgenic construct containing the cholera toxin gene under the control of the 6.5 kb promoter of the human dopamine receptor D1, DRD1, was injected into fertilized BALB/c X C57BL/6 hybrid fertilized eggs. Founder line 7 subsequently was established. Founder animals were backcrossed to BALB/cJ for 8 generations, then backcrossed to BALB/cAnNCrI for 22 generations before arriving at The Jackson Laboratory.
|Expressed Gene||ctxA, cholera enterotoxin, A subunit, Vibrio cholerae,|
|Site of Expression|
|Allele Name||transgene insertion 7, Frank H Burton|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Allele Synonym(s)||D1CT-7; Ticcy|
|Gene Symbol and Name||Tg(DRD1-ctxA)7Burt, transgene insertion 7, Frank H Burton|
|Promoter||DRD1, dopamine receptor D1, human|
|Expressed Gene||ctxA, cholera enterotoxin, A subunit, Vibrio cholerae,|
|Strain of Origin||BALB/c x C57BL/6|
|Molecular Note||The transgenic construct contains the cholera toxin intracellular enzymatic subunit A1 gene (ctxA) under the control of the 6.5 kb promoter of the human dopamine receptor D1, DRD1. Founder line 7 subsequently was established. Another female founder, 11, was produced but because this founder exhibited severe hyperreactivity in response to novel stimuli or introduction of potential mates, breeding this animal and estabilshing this line was precluded.|
|Mutations Made By|| |
Frank Burton, University of Minnesota
When maintaining a live colony, the recommended strategy is breeding wildtype females from the colony or BALB/cJ females with hemizygous males. The donating investigator recommends a large maintenance colony, suggesting that 15-20 symptomatic transgenic males each in breeding pairs with multiple BALB/c females is likely required to account for the variable breeding, viability obstacles, and reduced transgene inheritance of transgenic mice. In our experience only ~33% of pups produced these crosses inherit the transgene (~ 50% expected from Mendelian inheritance).
Transgenic females are fertile, and may be bred with either wildtype males from the colony or BALB/cJ males. They are not good mothers, however, due to their anxiety and grooming-biting phenotype, and may inadvertently injure or kill their pups. If a transgenic dam does get pregnant, all pups born should be transferred immediately to foster mothers to avoid the transgenic dams' cannibalistic behavior.
According to the donating investigator, homozygous transgenic mice are viable. Homozygous transgenic males, reportedly, are fertile, but homozygous females do not breed. We have never attempted to produce or breed homozygous transgenic mice at The Jackson Laboratory.
Transgenic mice may inadvertently but repeatedly injure cagemates(e.g., tail loss, skin wounds) by excessively biting during social grooming. Housing transgenic mice with multiple cagemates and including an interior domicile (mouse dome) in the cage as a retreat can help to minimize these injuries.
When using the C.Cg-Tg(DRD1-ctxA)7Burt/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008367 in your Materials and Methods section.
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