Description

Strain Information

Type Congenic; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Noncarrier x Hemizygote         (Female x Male) Species laboratory mouse Generation N8+N22+ (04-SEP-08)   Donating Investigator Frank 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 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. This mutant mouse strain may be useful in studies of Gilles De La Tourette Syndrome, obsessive-compulsive disorder (OCD) and Trichotillomania.

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
	Wild-type siblings from the colony
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

	Gilles De La Tourette Syndrome; GTS -
	Obsessive-Compulsive Disorder 1; OCD1 -

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      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 (MGI Ref ID J:55492)
  • transgenic mice attack intruder mice less frequently and show longer latency to attack than control littermates in a resident-intruder aggression assay
• hyperactivity (MGI Ref ID J:55492)
  • transgenic animals exhibit varying degrees of hyperlocomotion
• increased stereotypic behavior (MGI Ref ID J:55492)
  • mice exhibit stereotypic behaviors including increased repetitive locomotion, repetitive wall leaping, and gnawing whereas leaping is not observed in nontransgenic littermates
  • 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
  • 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
• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:55492)
  • brain is anatomically normal, with no discernible change in CNS morphology or neuron number
• abnormal olfactory cortex morphology (MGI Ref ID J:55492)
  • cAMP content is elevated 38% relative to controls
• abnormal somatosensory cortex morphology (MGI Ref ID J:55492)
  • cAMP content is elevated 38% relative to controls

Tg(DRD1-ctxA)7Burt/0

        C.Cg-Tg(DRD1-ctxA)7Burt

• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:133402)
  • mice display normal olfactory discrimination
• abnormal behavior (MGI Ref ID J:64883)
  • low-doses of MK-801 (non-competitive NMDA receptor antagonist) aggravate the repetitive climbing and leaping behavior of transgenic mice
  • 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
• abnormal involuntary movement (MGI Ref ID J:133268)
  • 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
  • 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
  • occurrence of tic flurries is highly increased in males compared to controls and to a lesser but significant extent in females
  • tics are significantly increased in juvenile transgenic animals and adult animals compared to controls
  • 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
• increased anxiety-related response (MGI Ref ID J:133401)
  • 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
• increased thigmotaxis (MGI Ref ID J:133401)
  • mice exhibit increased thigmotaxis in an open-field assay, compared to non-transgenic littermates
• increased stereotypic behavior (MGI Ref ID J:64883)
  • at high doses of MK-801, transgenic mice engage in more severe stereotypic/seizure behavior ( such as 'popping')
  • treatment with an AMPA receptor antagonist attenuates MK-801-induced stereotypic behaviors, but does not alter transgene-induced (repetitive climbing/leaping) behavior
  • mice display compulsion-like behaviors including prolonged behavior such as eating and repetitive behavior like leaping
  • presence of a novel odor or a familiar odor in the cage does not potentiate abnormal repetitive leaping-climbing behavior compared to controls
  • presence of an anxiogenic odor in the cage increases incidence of leaping-climbing 2-fold relative to controls; anxiogenic odor potentiates compulsion-like behavior
  • 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

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

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 Origin		BALB/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, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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]

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

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred by wildtype female crossed to hemizygous males. The Donating Investigator has bred hemizygous male X wildtype female BALB/c for 30 generations. 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.
Mating System	Noncarrier x Hemizygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development and On Hold

Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type siblings from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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