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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?+2p (06-JUN-04)   Donating Investigator Heiner Westphal,   National Institutes of Health

Description
Mice homozygous for the Drd1a^tm1Jcd targeted mutation exhibit growth retardation and show down-regulated expression of dynorphin and substance P. They also show behavioral anomolies in spatial learning, movement initiation, and responses to new stimuli. Administration of cocaine to homozygotes does not activate locomotion or up-regulate immediate early gene (IEG) expression; however, dopamine receptor-2-dependent IEG changes are intact. Acute cocaine administration increases substance P levels. Failure of locomotor activation is also seen with repeated amphetamine treatment. Dopamine receptor D1a deficient mice do retain cocaine-conditioned place preference. Please Note: Growth retardation, which may be due to abnormal or delayed tooth formation, is avoided if homozygotes are fed either hydrated or crushed grain from ~2-10 weeks of age. Homozygotes do appear thinner than wildtypes and have a very slight halting gait (unpublished observations, The Jackson Laboratory). Heterozygous mice are unaffected.

Development
This targeted mutant was made by Dr. John Drago in the laboratory of Dr. Heiner Westphal of the National Institute of Child Health and Human Development. A targeting vector was used which resulted in the neomycin-resistant gene (neo) replacing all coding sequences of the Drd1 gene. 129-derived J1 ES cells were used.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Related Strains

Strains carrying   Drd1a^tm1Jcd allele

002959

B6.129S4-Drd1atm1Jcd/J

View Strains carrying   Drd1a^tm1Jcd     (1 strain)

Strains carrying other alleles of Drd1a

007586

B6;129S4-Drd1atm2Rpa/J

View Strains carrying other alleles of Drd1a     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Drd1a^tm1Jcd/Drd1a⁺

        involves: 129S4/SvJae

• behavior/neurological phenotype
• abnormal contextual conditioning (MGI Ref ID J:67395)
  • 3-5 month old mice exhibit delayed extinction of conditioned fear responses compared to wild-type; mice display normal acquisition of contextual fear conditioning; null mice do not show a decline in freeaing responses over three days as do the wild-type; a significantly higher her percentage of contextual freezing responses is observed for up to 90 days
• abnormal passive avoidance behavior (MGI Ref ID J:67395)
  • after confinement for 1 minute to the shock-paired chamber, 3 to 5 month old heterozygous mice show less of a decline in latency to enter the conditioning chamber compared to wild-type

Drd1a^tm1Jcd/Drd1a^tm1Jcd

        involves: 129S4/SvJae * C57BL/6

• behavior/neurological phenotype
• decreased vertical activity (MGI Ref ID J:22076)
  • 5-6 week old mutants exhibit significantly fewer rearing events than wild-type
• hunched posture (MGI Ref ID J:22076)
  • by weaning, mice have hunched posture
• growth/size phenotype
• decreased body weight (MGI Ref ID J:22076)
  • mice that are separated from heterozygous and wild-type littermates fed moistened lab chow appear healthy but only gain 70% of weight that sex-matched littermates reach by 6 weeks of age
• postnatal growth retardation (MGI Ref ID J:22076)
  • mice are normal with respect to wild-type up to 2 weeks of age, but are significantly growth retarded by weaning age; mice appear sickly and majority do not gain weight
• life span-post-weaning/aging
• premature death (MGI Ref ID J:22076)
  • majority of mice die within 1 week after weaning
• skin/coat/nails phenotype
• disheveled coat (MGI Ref ID J:22076)
  • by weaning, mice have poorly groomed coat

Drd1a^tm1Jcd/Drd1a^tm1Jcd

        involves: 129S4/SvJae

• behavior/neurological phenotype
• abnormal contextual conditioning (MGI Ref ID J:67395)
  • 3-5 month old mice exhibit delayed extinction of conditioned fear responses compared to wild-type; mice display normal acquisition of contextual fear conditioning; null mice do not show a decline in freeaing responses over three days as do the wild-type; a significantly higher her percentage of contextual freezing responses is observed for up to 90 days
• abnormal passive avoidance behavior (MGI Ref ID J:67395)
  • 3-5 month old nulls maintain enhanced step-through latencies for up to 45 days post shock-conditioning
  • after confinement for 1 minute to the shock-paired chamber, null mice show less of a decline in latency to enter the conditioning chamber compared to wild-type
• abnormal spatial learning (MGI Ref ID J:102603)
  • 3-5 month old null mice exhibit a spatial learning deficit as shown by longer latencies to locate a hidden platmform in the initial acquisition phase
  • in the first probe trial with an absent platform conducted 24 hours after the acquisiton trials, null mice display less selective searching behavior for an absent platform and less time in the target quadrant (40% for control, 27% for nulls); on reversal trials with the platform in a new location, null animals have longer escape latencies than control over the course of 12 trials
  • in a second probe trial with the platform removed, the time spent in the target quadrant by null mice is 31% compared to 50% by controls and had a reduced number of annulus crossings through the former location of the platform
  • in trials with a visual cue of the platform location, null mice showed longer escape latencies during trials 4-12, then showed similar performance to conrols
• growth/size phenotype
• decreased body size (MGI Ref ID J:102603)
  • nulls are 20-30% smaller than heterozygotes or wild-type

View Research Applications

Research Applications

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

Neurobiology Research
Receptor Defects (dopamine receptor)

Drd1a^tm1Jcd related

Neurobiology Research
Cortical Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Drd1atm1Jcd
Allele Name		targeted mutation 1, John Drago
Allele Type		Targeted (knock-out)
Common Name(s)		D1-; D1A-; Dlr-;
Mutation Made By		John Drago,   National Institutes of Health
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Drd1a, dopamine receptor D1A
Chromosome		13
Gene Common Name(s)		C030036C15Rik; D1 receptor; D1a; DADR; Drd-1; Drd1; G-protein coupled receptor 15; Gpcr15; RIKEN cDNA C030036C15 gene; dopamine receptor 1;
General Note		Homozygous mutant mice suffer growth retardation, and die shortly after weaning unless given hydrated food. Survivors show normal coordination. D1A receptor binding was absent in homozygous mutants, although the neurons normally expressing D1A receptors are present. Tachykinin mRNAs, normally found in D1A-positive striatal neurons, are expressed at a reduced level. Enkephalin, normally colocalized in expression with D2 receptors, is expressed at normal levels (J:22076).
Molecular Note		A neomycin resistance cassette replaced 0.75kb of sequence encoding the fifth transmembrane domain and third intracytoplasmic loop. [MGI Ref ID J:22076]

Genotyping

Genotyping Information

Genotyping Protocols

Drd1a^tm1Jcd, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Drago J; Gerfen CR; Lachowicz JE; Steiner H; Hollon TR; Love PE; Ooi GT; Grinberg A; Lee EJ; Huang SP; Bartlett PF; Jose PA; Sibley DR; Westphal H. 1994. Altered striatal function in a mutant mouse lacking D1A dopamine receptors. Proc Natl Acad Sci U S A 91(26):12564-8. [PubMed: 7809078]  [MGI Ref ID J:22076]

Additional References

Levine MS; Altemus KL; Cepeda C; Cromwell HC; Crawford C; Ariano MA; Drago J; Sibley DR; Westphal H. 1996. Modulatory actions of dopamine on NMDA receptor-mediated responses are reduced in D1A-deficient mutant mice. J Neurosci 16(18):5870-82. [PubMed: 8795639]  [MGI Ref ID J:35286]

Drd1a^tm1Jcd related

Beaulieu JM; Tirotta E; Sotnikova TD; Masri B; Salahpour A; Gainetdinov RR; Borrelli E; Caron MG. 2007. Regulation of Akt signaling by D2 and D3 dopamine receptors in vivo. J Neurosci 27(4):881-5. [PubMed: 17251429]  [MGI Ref ID J:117785]

Bender M; Drago J; Rivkees SA. 1997. D1 receptors mediate dopamine action in the fetal suprachiasmatic nuclei: studies of mice with targeted deletion of the D1 dopamine receptor gene. Brain Res Mol Brain Res 49(1-2):271-7. [PubMed: 9387887]  [MGI Ref ID J:43604]

Cannon CM; Scannell CA; Palmiter RD. 2005. Mice lacking dopamine D1 receptors express normal lithium chloride-induced conditioned taste aversion for salt but not sucrose. Eur J Neurosci 21(9):2600-4. [PubMed: 15932618]  [MGI Ref ID J:101069]

Clifford JJ; Tighe O; Croke DT; Kinsella A; Sibley DR; Drago J; Waddington JL. 1999. Conservation of behavioural topography to dopamine D1-like receptor agonists in mutant mice lacking the D1A receptor implicates a D1-like receptor not coupled to adenylyl cyclase. Neuroscience 93(4):1483-9. [PubMed: 10501473]  [MGI Ref ID J:59466]

Clifford JJ; Tighe O; Croke DT; Sibley DR; Drago J; Waddington JL. 1998. Topographical evaluation of the phenotype of spontaneous behaviour in mice with targeted gene deletion of the D1A dopamine receptor: paradoxical elevation of grooming syntax. Neuropharmacology 37(12):1595-602. [PubMed: 9886682]  [MGI Ref ID J:52350]

Crandall JE; McCarthy DM; Araki KY; Sims JR; Ren JQ; Bhide PG. 2007. Dopamine receptor activation modulates GABA neuron migration from the basal forebrain to the cerebral cortex. J Neurosci 27(14):3813-22. [PubMed: 17409246]  [MGI Ref ID J:121219]

Crawford CA; Drago J; Watson JB; Levine MS. 1997. Effects of repeated amphetamine treatment on the locomotor activity of the dopamine D1A-deficient mouse. Neuroreport 8(11):2523-7. [PubMed: 9261820]  [MGI Ref ID J:45740]

Cromwell HC; Berridge KC; Drago J; Levine MS. 1998. Action sequencing is impaired in D1A-deficient mutant mice. Eur J Neurosci 10(7):2426-32. [PubMed: 9749770]  [MGI Ref ID J:50990]

Drago F; Contarino A; Busa L. 1999. The expression of neuropeptide-induced excessive grooming behavior in dopamine D1 and D2 receptor-deficient mice. Eur J Pharmacol 365(2-3):125-31. [PubMed: 9988094]  [MGI Ref ID J:56015]

El-Ghundi M; Fletcher PJ; Drago J; Sibley DR; O'Dowd BF; George SR. 1999. Spatial learning deficit in dopamine D(1) receptor knockout mice. Eur J Pharmacol 383(2):95-106. [PubMed: 10585522]  [MGI Ref ID J:102603]

El-Ghundi M; O'Dowd BF; Erclik M; George SR. 2003. Attenuation of sucrose reinforcement in dopamine D1 receptor deficient mice. Eur J Neurosci 17(4):851-62. [PubMed: 12603275]  [MGI Ref ID J:107997]

El-Ghundi M; O'Dowd BF; George SR. 2001. Prolonged fear responses in mice lacking dopamine D(1) receptor. Brain Res 892(1):86-93. [PubMed: 11172752]  [MGI Ref ID J:67395]

Friedman E; Jin LQ; Cai GP; Hollon TR; Drago J; Sibley DR; Wang HY. 1997. D1-like dopaminergic activation of phosphoinositide hydrolysis is independent of D1A dopamine receptors: evidence from D1A knockout mice. Mol Pharmacol 51(1):6-11. [PubMed: 9016340]  [MGI Ref ID J:38464]

Herve D; Le Moine C; Corvol JC; Belluscio L; Ledent C; Fienberg AA; Jaber M; Studler JM; Girault JA. 2001. Galpha(olf) levels are regulated by receptor usage and control dopamine and adenosine action in the striatum. J Neurosci 21(12):4390-9. [PubMed: 11404425]  [MGI Ref ID J:123805]

Huang YY; Simpson E; Kellendonk C; Kandel ER. 2004. Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors. Proc Natl Acad Sci U S A 101(9):3236-41. [PubMed: 14981263]  [MGI Ref ID J:88654]

Ito M; Numachi Y; Ohara A; Sora I. 2008. Hyperthermic and lethal effects of methamphetamine: Roles of dopamine D1 and D2 receptors. Neurosci Lett 438(3):327-9. [PubMed: 18486343]  [MGI Ref ID J:137069]

Karasinska JM; George SR; Cheng R; O'Dowd BF. 2005. Deletion of dopamine D1 and D3 receptors differentially affects spontaneous behaviour and cocaine-induced locomotor activity, reward and CREB phosphorylation. Eur J Neurosci 22(7):1741-50. [PubMed: 16197514]  [MGI Ref ID J:102922]

Karasinska JM; George SR; El-Ghundi M; Fletcher PJ; O'Dowd BF. 2000. Modification of dopamine D(1) receptor knockout phenotype in mice lacking both dopamine D(1) and D(3) receptors. Eur J Pharmacol 399(2-3):171-81. [PubMed: 10884517]  [MGI Ref ID J:102600]

Karper PE; De la Rosa H; Newman ER; Krall CM; Nazarian A; McDougall SA; Crawford CA. 2002. Role of D1-like receptors in amphetamine-induced behavioral sensitization: a study using D1A receptor knockout mice. Psychopharmacology (Berl) 159(4):407-14. [PubMed: 11823893]  [MGI Ref ID J:103950]

Karper PE; Nazarian A; Crawford CA; Drago J; McDougall SA. 2000. Role of dopamine D(1) receptors for kappa-opioid-mediated locomotor activity and antinociception during the preweanling period: a study using D(1) receptor knockout mice. Physiol Behav 68(4):585-90. [PubMed: 10713301]  [MGI Ref ID J:96590]

Kobayashi M; Iaccarino C; Saiardi A; Heidt V; Bozzi Y; Picetti R; Vitale C; Westphal H; Drago J; Borrelli E. 2004. Simultaneous absence of dopamine D1 and D2 receptor-mediated signaling is lethal in mice. Proc Natl Acad Sci U S A 101(31):11465-70. [PubMed: 15272078]  [MGI Ref ID J:91781]

Leonard SK; Ferry-Leeper P; Mailman RB. 2006. Low affinity binding of the classical D(1) antagonist SCH23390 in rodent brain: Potential interaction with A(2A) and D(2)-like receptors. Brain Res 1117(1):25-37. [PubMed: 16962565]  [MGI Ref ID J:114543]

Levine MS; Altemus KL; Cepeda C; Cromwell HC; Crawford C; Ariano MA; Drago J; Sibley DR; Westphal H. 1996. Modulatory actions of dopamine on NMDA receptor-mediated responses are reduced in D1A-deficient mutant mice. J Neurosci 16(18):5870-82. [PubMed: 8795639]  [MGI Ref ID J:35286]

Matthies H; Becker A; Schroeder H; Kraus J; Hollt V; Krug M. 1997. Dopamine D1-deficient mutant mice do not express the late phase of hippocampal long-term potentiation. Neuroreport 8(16):3533-5. [PubMed: 9427321]  [MGI Ref ID J:103731]

McNamara FN; Clifford JJ; Tighe O; Kinsella A; Drago J; Croke DT; Waddington JL. 2003. Congenic D1A dopamine receptor mutants: ethologically based resolution of behavioural topography indicates genetic background as a determinant of knockout phenotype. Neuropsychopharmacology 28(1):86-99. [PubMed: 12496944]  [MGI Ref ID J:106126]

Miner LL; Drago J; Chamberlain PM; Donovan D; Uhl GR. 1995. Retained cocaine conditioned place preference in D1 receptor deficient mice. Neuroreport 6(17):2314-6. [PubMed: 8747144]  [MGI Ref ID J:117915]

Miyamoto S; Mailman RB; Lieberman JA; Duncan GE. 2001. Blunted brain metabolic response to ketamine in mice lacking D(1A) dopamine receptors. Brain Res 894(2):167-80. [PubMed: 11251190]  [MGI Ref ID J:68124]

Narayanan S; Lam H; Christian L; Levine MS; Grandy D; Rubinstein M; Maidment NT. 2004. Endogenous opioids mediate basal hedonic tone independent of dopamine D-1 or D-2 receptor activation. Neuroscience 124(1):241-6. [PubMed: 14960355]  [MGI Ref ID J:90516]

Parish CL; Finkelstein DI; Drago J; Borrelli E; Horne MK. 2001. The role of dopamine receptors in regulating the size of axonal arbors. J Neurosci 21(14):5147-57. [PubMed: 11438590]  [MGI Ref ID J:70177]

Ralph-Williams RJ; Lehmann-Masten V; Otero-Corchon V; Low MJ; Geyer MA. 2002. Differential effects of direct and indirect dopamine agonists on prepulse inhibition: a study in D1 and D2 receptor knock-out mice. J Neurosci 22(21):9604-11. [PubMed: 12417685]  [MGI Ref ID J:111572]

Seeman P; Weinshenker D; Quirion R; Srivastava LK; Bhardwaj SK; Grandy DK; Premont RT; Sotnikova TD; Boksa P; El-Ghundi M; O'dowd BF; George SR; Perreault ML; Mannisto PT; Robinson S; Palmiter RD; Tallerico T. 2005. Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis. Proc Natl Acad Sci U S A 102(9):3513-8. [PubMed: 15716360]  [MGI Ref ID J:96985]

Short JL; Ledent C; Borrelli E; Drago J; Lawrence AJ. 2006. Genetic interdependence of adenosine and dopamine receptors: Evidence from receptor knockout mice. Neuroscience 139(2):661-70. [PubMed: 16476524]  [MGI Ref ID J:107738]

Smith DR; Striplin CD; Geller AM; Mailman RB; Drago J; Lawler CP ; Gallagher M. 1998. Behavioural assessment of mice lacking D1A dopamine receptors. Neuroscience 86(1):135-46. [PubMed: 9692749]  [MGI Ref ID J:48769]

Stanwood GD; Parlaman JP; Levitt P. 2005. Anatomical abnormalities in dopaminoceptive regions of the cerebral cortex of dopamine D1 receptor mutant mice. J Comp Neurol 487(3):270-82. [PubMed: 15892099]  [MGI Ref ID J:99709]

Stanwood GD; Parlaman JP; Levitt P. 2006. Genetic or pharmacological inactivation of the dopamine D1 receptor differentially alters the expression of regulator of G-protein signalling (Rgs) transcripts. Eur J Neurosci 24(3):806-18. [PubMed: 16930410]  [MGI Ref ID J:112924]

Stipanovich A; Valjent E; Matamales M; Nishi A; Ahn JH; Maroteaux M; Bertran-Gonzalez J; Brami-Cherrier K; Enslen H; Corbille AG; Filhol O; Nairn AC; Greengard P; Herve D; Girault JA. 2008. A phosphatase cascade by which rewarding stimuli control nucleosomal response. Nature 453(7197):879-84. [PubMed: 18496528]  [MGI Ref ID J:137074]

Tomiyama K; McNamara FN; Clifford JJ; Kinsella A; Drago J; Tighe O; Croke DT; Koshikawa N; Waddington JL. 2002. Phenotypic resolution of spontaneous and D1-like agonist-induced orofacial movement topographies in congenic dopamine D1A receptor 'knockout' mice. Neuropharmacology 42(5):644-52. [PubMed: 11985822]  [MGI Ref ID J:97339]

Vinkers CH; Risbrough VB; Geyer MA; Caldwell S; Low MJ; Hauger RL. 2007. Role of dopamine D1 and D2 receptors in CRF-induced disruption of sensorimotor gating. Pharmacol Biochem Behav 86(3):550-8. [PubMed: 17324452]  [MGI Ref ID J:124479]

Wong JY; Clifford JJ; Massalas JS; Finkelstein DI; Horne MK; Waddington JL; Drago J. 2003. Neurochemical changes in dopamine D1, D3 and D1/D3 receptor knockout mice. Eur J Pharmacol 472(1-2):39-47. [PubMed: 12860471]  [MGI Ref ID J:103739]

Wong JY; Clifford JJ; Massalas JS; Kinsella A; Waddington JL; Drago J. 2003. Essential conservation of D1 mutant phenotype at the level of individual topographies of behaviour in mice lacking both D1 and D3 dopamine receptors. Psychopharmacology (Berl) 167(2):167-73. [PubMed: 12652349]  [MGI Ref ID J:103886]

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

Colony Maintenance

Breeding & Husbandry	This strain is maintained by mating homozygous siblings.
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	None Available
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.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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