Strain Name:

C.Cg-Tg(DRD1-ctxA)7Burt/J

Stock Number:

008367

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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.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN8+N22+F2pN1
Generation Definitions
 
Donating Investigator Frank H Burton,   University of Minnesota

Description
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%).

Development
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.

Control Information

  Control
   Noncarrier
   000651 BALB/cJ
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Gilles De La Tourette Syndrome; GTS
Obsessive-Compulsive Disorder; OCD
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Tg(DRD1-ctxA)7Burt/0

        either: C.Cg-Tg(DRD1-ctxA)7Burt or (involves: BALB/c * C57BL/6)
  • behavior/neurological phenotype
  • decreased aggression towards mice
    • transgenic mice attack intruder mice less frequently and show longer latency to attack than control littermates in a resident-intruder aggression assay   (MGI Ref ID J:55492)
  • hyperactivity
    • transgenic animals exhibit varying degrees of hyperlocomotion   (MGI Ref ID J:55492)
  • increased stereotypic behavior
    • mice exhibit stereotypic behaviors including increased repetitive locomotion, repetitive wall leaping, and gnawing whereas leaping is not observed in nontransgenic littermates   (MGI Ref ID J:55492)
    • transgenic mice exhibit perseverative episodes of all normal behaviors, consisting of long-duration episodes of stationary single-state behaviors (eating, drinking, grooming, etc) and long-duration episodes of reiterated locomotor-dependent (two state) behavior (ie. locomote- forage- locomote- explore); behavioral duration is about 3-fold greater than in control animals; stationary behavior episodes are also 3-fold greater   (MGI Ref ID J:55492)
    • both males and females display nonaggressive, repetitive biting of littermates; such episodes occur during episodes of social grooming, not during aggressive displays or fighting and begins when mice are less than 3 weeks of age   (MGI Ref ID J:55492)
  • nervous system phenotype
  • *normal* nervous system phenotype
    • brain is anatomically normal, with no discernible change in CNS morphology or neuron number   (MGI Ref ID J:55492)
    • abnormal olfactory cortex morphology
      • cAMP content is elevated 38% relative to controls   (MGI Ref ID J:55492)
    • abnormal somatosensory cortex morphology
      • cAMP content is elevated 38% relative to controls   (MGI Ref ID J:55492)

Tg(DRD1-ctxA)7Burt/0

        C.Cg-Tg(DRD1-ctxA)7Burt
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • mice display normal olfactory discrimination   (MGI Ref ID J:133402)
    • abnormal behavior
      • low-doses of MK-801 (non-competitive NMDA receptor antagonist) aggravate the repetitive climbing and leaping behavior of transgenic mice   (MGI Ref ID J:64883)
      • mice engage in obsessive-compulsive disorder-like behavior such as prolonged episodes of essentially normal behaviors; total behavior repertoire and average number of behaviors is similar to wild-type   (MGI Ref ID J:133401)
      • abnormal involuntary movement
        • repetitive twitches (tics) occur at 5-fold higher frequency compared to controls which show twitches infrequently with tics a greater increased frequency observed in females   (MGI Ref ID J:133268)
        • tic complexity is increased compared to controls with a higher percentage of non-shaking tics observed; this is statistically significant in females and approaches significance in males relative to control   (MGI Ref ID J:133268)
        • occurrence of tic flurries is highly increased in males compared to controls and to a lesser but significant extent in females   (MGI Ref ID J:133268)
        • tics are significantly increased in juvenile transgenic animals and adult animals compared to controls   (MGI Ref ID J:133268)
        • clonidine (non-cataleptic drug) treatment reduces incidence of tics without affecting locomotor behavior similar to its effects in humans with Tourette's + obsessive compulsive disorder   (MGI Ref ID J:133268)
      • increased anxiety-related response
        • in light-dark assay, mice display longer latency to first transit from dark chamber and show tendency to spend less time in lighted (reduced transits) areas than controls   (MGI Ref ID J:133401)
        • increased thigmotaxis
          • mice exhibit increased thigmotaxis in an open-field assay, compared to non-transgenic littermates   (MGI Ref ID J:133401)
      • increased stereotypic behavior
        • at high doses of MK-801, transgenic mice engage in more severe stereotypic/seizure behavior ( such as 'popping')   (MGI Ref ID J:64883)
        • treatment with an AMPA receptor antagonist attenuates MK-801-induced stereotypic behaviors, but does not alter transgene-induced (repetitive climbing/leaping) behavior   (MGI Ref ID J:64883)
        • mice display compulsion-like behaviors including prolonged behavior such as eating and repetitive behavior like leaping   (MGI Ref ID J:133402)
        • presence of a novel odor or a familiar odor in the cage does not potentiate abnormal repetitive leaping-climbing behavior compared to controls   (MGI Ref ID J:133402)
        • presence of an anxiogenic odor in the cage increases incidence of leaping-climbing 2-fold relative to controls; anxiogenic odor potentiates compulsion-like behavior   (MGI Ref ID J:133402)
        • upon injection with yohimbine, transgenic animals display a significant increase abnormal repetitive leaping/climbing behavior compared to saline-injected control transgenics, but duration of perseverative (prolonged) episodes is not exacerbated   (MGI Ref ID J:133401)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Neurobiology Research
Behavioral and Learning Defects
      high anxiety

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(DRD1-ctxA)7Burt
Allele Name transgene insertion 7, Frank H Burton
Allele Type Transgenic (random, expressed)
Common Name(s) D1CT-7; Ticcy;
Mutation Made By Frank Burton,   University of Minnesota
Strain of OriginBALB/c x C57BL/6
Expressed Gene ctxA, cholera enterotoxin, A subunit, Vibrio cholerae,
Promoter DRD1, dopamine receptor D1, human
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. [MGI Ref ID J:55492]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(DRD1-ctxA)7Burt, Separated PCR
Tg(DRD1-ctxA)7Burt, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Campbell KM; de Lecea L; Severynse DM; Caron MG; McGrath MJ; Sparber SB; Sun LY; Burton FH. 1999. OCD-Like behaviors caused by a neuropotentiating transgene targeted to cortical and limbic D1+ neurons. J Neurosci 19(12):5044-53. [PubMed: 10366637]  [MGI Ref ID J:55492]

McGrath MJ; Campbell KM; Parks CR; Burton FH. 2000. Glutamatergic drugs exacerbate symptomatic behavior in a transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder Brain Res 877(1):23-30. [PubMed: 10980239]  [MGI Ref ID J:64883]

Additional References

Tg(DRD1-ctxA)7Burt related

Campbell KM; McGrath MJ; Burton FH. 1999. Behavioral effects of cocaine on a transgenic mouse model of cortical-limbic compulsion. Brain Res 833(2):216-24. [PubMed: 10375697]  [MGI Ref ID J:133269]

Felling RJ; Singer HS. 2011. Neurobiology of tourette syndrome: current status and need for further investigation. J Neurosci 31(35):12387-95. [PubMed: 21880899]  [MGI Ref ID J:176227]

McGrath MJ; Campbell KM; Burton FH. 1999. The role of cognitive and affective processing in a transgenic mouse model of cortical-limbic neuropotentiated compulsive behavior. Behav Neurosci 113(6):1249-56. [PubMed: 10636303]  [MGI Ref ID J:133402]

McGrath MJ; Campbell KM; Veldman MB; Burton FH. 1999. Anxiety in a transgenic mouse model of cortical-limbic neuro-potentiated compulsive behavior. Behav Pharmacol 10(5):435-43. [PubMed: 10780249]  [MGI Ref ID J:133401]

Nordstrom EJ; Burton FH. 2002. A transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder circuitry. Mol Psychiatry 7(6):617-25, 524. [PubMed: 12140785]  [MGI Ref ID J:133268]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen 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.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2450.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3185.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Noncarrier
   000651 BALB/cJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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