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Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?+3 Donating Investigator W. Scott Young III, National Institute of Mental Health Description
Mice homozygous for the Oxttm1Wsy targeted mutation are viable and fertile. Females are able to successfully mate, deliver and produce milk however milk injection is impaired. Pups do not successfully suckle and must be fostered to survive. Oxytocin injection restores milk injection in response to suckling. Homozygotes displayed reduced aggressive behavior relative to heterozygotes and wild-type mice.Development
This strain was developed in the laboratory of Dr. W. Scott Young at the National Institute of Mental Health. Exons 2 and 3 of the oxytocin gene were replaced with a vector containing the neomycin resistance gene.
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Oxt
006043 B6;SJL-Tg(Oxt/EGFP)AI03Wsy/J View Strains carrying other alleles of Oxt (1 strain)
Genetic Quality Control Annual Report
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Oxttm1Wsy/Oxt+
involves: 129S/SvEv * C57BL/6
- behavior/neurological phenotype
- *normal* behavior/neurological phenotype (MGI Ref ID J:41146)
- heterozygotes exhibit neither significant differences in aggressiveness and exploratory activity nor sensorimotor deficits in olfaction, visual acuity, coordination or forearm strength tasks
- digestive/alimentary phenotype
- abnormal defecation (MGI Ref ID J:41146)
- heterozygotes display a significantly reduced frequency of defecation relative to wild-type mice
Oxttm1Wsy/Oxttm1Wsy
involves: 129S/SvEv * C57BL/6
- endocrine/exocrine gland phenotype
- abnormal lactation (MGI Ref ID J:36926)
- abnormal milk ejection (MGI Ref ID J:91657)
- homozygous mice are grossly normal and fertile, carry normal-sized litters and produce milk, but fail to eject milk in response to suckling
- as a result, newborn pups fail to survive for >24 hrs, dying without milk in their stomachs, despite apparently normal suckling
- i.p. injection of oxytocin into homozygous mutant dams restores milk ejection in response to suckling
- abnormal mammary gland growth during lactation (MGI Ref ID J:91657)
- at parturition, homozygous dams show normal alveolar density and mammary epithelial cell differentiation
- however, shortly after parturition, homozygous dams display partially involuted mammary tissue, despite suckling and the presence of systemic lactogenic hormones
- in addition, homozygous dams fail to exhibit post-partum DNA synthesis and proliferation of alveolar cells
- renal/urinary system phenotype
- *normal* renal/urinary system phenotype (MGI Ref ID J:91657)
- male homozygotes exhibit normal plasma osmolarities and are able to concentrate their urine after 24 hrs of water deprovation
- reproductive system phenotype
- abnormal lactation (MGI Ref ID J:36926)
- abnormal milk ejection (MGI Ref ID J:91657)
- homozygous mice are grossly normal and fertile, carry normal-sized litters and produce milk, but fail to eject milk in response to suckling
- as a result, newborn pups fail to survive for >24 hrs, dying without milk in their stomachs, despite apparently normal suckling
- i.p. injection of oxytocin into homozygous mutant dams restores milk ejection in response to suckling
- abnormal mammary gland growth during lactation (MGI Ref ID J:91657)
- at parturition, homozygous dams show normal alveolar density and mammary epithelial cell differentiation
- however, shortly after parturition, homozygous dams display partially involuted mammary tissue, despite suckling and the presence of systemic lactogenic hormones
- in addition, homozygous dams fail to exhibit post-partum DNA synthesis and proliferation of alveolar cells
- behavior/neurological phenotype
- abnormal circadian rhythm (MGI Ref ID J:72051)
- under baseline conditions, homozygous males display an abnormal circadian rhythm of salt and water intake
- abnormal drinking behavior (MGI Ref ID J:72051)
- under baseline conditions, homozygous males show no significant differences in water consumption relative to wild-type mice
- however, mutant males initiate water intake 3 hrs earlier in the light/dark cycle relative to wild-type males
- abnormal food preference (MGI Ref ID J:72051)
- under baseline conditions, homozygous males exhibit a 4-6-fold increase in salt licking activity (licks/24 hrs) and salt (2% NaCl) consumption relative to wild-type males
- salt licking activity is prominent during the dark period, as expected
- voluntary consumption of a hypertonic salt solution is not driven by plasma hyperosmolarity, as no changes in ionic concentrations are observed
- despite increased 2% NaCl consumption, homozygotes are able to maintain a balance of intake and excretion
- decreased aggression (MGI Ref ID J:91657)
- homozygotes display reduced aggression in agonistic bouts within a neutral arena, with significantly less time spent in aggressive encounters and significantly shorter aggressive attacks
- notably, homozygotes exhibit a greater reduction in agonistic interactions in the neutral arena than in the resident-intruder paradigm
- decreased grooming behavior (MGI Ref ID J:41146)
- homozygotes exhibit neither significant differences in exploratory activity in the open field test nor sensorimotor deficits in olfaction, visual acuity, coordination or forearm strength tasks
- however, homozygotes spend significantly less time autogrooming in the open field than wild-type mice
- cardiovascular system phenotype
- abnormal cardiovascular system physiology (MGI Ref ID J:83910)
- in response to depressor challenges, homozygotes show a significant reduction in maximal bradycardia and a potentiation of reflex tachycardia, in accordance with an increased sympathetic reserve to the heart
- after beta 1-adrenergic and cholinergic blockade, homozygotes show a normal magnitude of sympathetic and vagal tone to the heart and periphery; however, mutants exhibit an upward shift of sympathetic tone to higher heart rate values resulting in larger responses to cholinergic blockade
- hypotension (MGI Ref ID J:83910)
- homozygotes exhibit a mild but consistent hypotension (102 ± 3 vs. 110 ± 3 mmHg), with no significant changes in baseline heart rate relative to wild-type mice
- nervous system phenotype
- abnormal baroreceptor physiology (MGI Ref ID J:83910)
- homozygotes exhibit a >3-fold increase in the gain of reflex as well as a notable decrease in the operating pressure range of baroreceptor reflex function
Oxttm1Wsy/Oxttm1Wsy
B6;129S-Oxttm1Wsy/J
- behavior/neurological phenotype
- abnormal anxiety-related response (MGI Ref ID J:83709)
- at 6-11 months, homozygous females (from F5 and F6) display increased anxiety-like behavior in the elevated plus-maze (EPM), despite a normal overall locomotor activity
- in females, enhanced anxiety is reversed by icv administration of exogenous oxytocin; furthermore, central infusion of an oxytocin receptor antagonist prior to the administration of synthetic oxytocin blocks the anxiolytic effect
- in contrast, age-matched homozygous males exhibit reduced anxiety-like behavior in the EPM relative to wild-type males
- abnormal eating/drinking behavior (MGI Ref ID J:98510)
- after an 18-h fast, homozygous males consume slightly - but not significantly - less chow during a 60-min refeeding period when dehydrated compared with their intake when euhydrated
- in mutants, attenuated dehydration anorexia is accompanied by reduced Fos expression in the hindbrain dorsal vagal complex
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Oxttm1Wsy related
Cancer Research
Genes Regulating Growth and Proliferation
Endocrine Deficiency Research
Hypothalamus/Pituitary Defects
Mammary Gland Defects
Neurobiology Research
Behavioral and Learning Defects
| Allele Symbol | Oxttm1Wsy | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, W Scott Young III | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | OT-; OTKO -; | ||
| Mutation Made By | W. Scott Young III, National Institute of Mental Health | ||
| Strain of Origin | 129S/SvEv-Gpi1 | ||
| ES Cell Line Name | CCE/EK.CCE | ||
| ES Cell Line Strain | 129S/SvEv-Gpi1 | ||
| Gene Symbol and Name | Oxt, oxytocin | ||
| Chromosome | 2 | ||
| Gene Common Name(s) | MGC126890; MGC126892; OT; OT-NPI; Oxy; | ||
| Molecular Note | The gene was disrupted using neomycin resistance cassette. The vector replaced sequences encoding the last two exons. Hybridization histochemistry and immunocytochemistry were used to demonstrate the lack of transcript and protein in homozygous mutant animals. [MGI Ref ID J:36926] | ||
Genotyping Protocols
Oxttm1Wsy, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
Young WS 3rd; Shepard E; Amico J; Hennighausen L; Wagner KU; LaMarca ME; McKinney C; Ginns EI. 1996. Deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition. J Neuroendocrinol 8(11):847-53. [PubMed: 8933362] [MGI Ref ID J:36926]
Amico JA; Morris M; Vollmer RR. 2001. Mice deficient in oxytocin manifest increased saline consumption following overnight fluid deprivation. Am J Physiol Regul Integr Comp Physiol 281(5):R1368-73. [PubMed: 11641104] [MGI Ref ID J:72554]
DeVries AC; Young WS 3rd; Nelson RJ. 1997. Reduced aggressive behaviour in mice with targeted disruption of the oxytocin gene. J Neuroendocrinol 9(5):363-8. [PubMed: 9181490] [MGI Ref ID J:41146]
Mantella RC; Vollmer RR; Li X; Amico JA. 2003. Female oxytocin-deficient mice display enhanced anxiety-related behavior. Endocrinology 144(6):2291-6. [PubMed: 12746288] [MGI Ref ID J:83709]
Michelini LC; Marcelo MC; Amico J; Morris M. 2003. Oxytocinergic regulation of cardiovascular function: studies in oxytocin-deficient mice. Am J Physiol Heart Circ Physiol 284(6):H2269-76. [PubMed: 12531722] [MGI Ref ID J:83910]
Puryear R; Rigatto KV; Amico JA; Morris M. 2001. Enhanced salt intake in oxytocin deficient mice. Exp Neurol 171(2):323-8. [PubMed: 11573985] [MGI Ref ID J:72051]
Oxttm1Wsy relatedAmico JA; Cai HM; Vollmer RR. 2008. Corticosterone release in oxytocin gene deletion mice following exposure to psychogenic versus non-psychogenic stress. Neurosci Lett 442(3):262-6. [PubMed: 18625285] [MGI Ref ID J:140241]
Amico JA; Morris M; Vollmer RR. 2001. Mice deficient in oxytocin manifest increased saline consumption following overnight fluid deprivation. Am J Physiol Regul Integr Comp Physiol 281(5):R1368-73. [PubMed: 11641104] [MGI Ref ID J:72554]
Amico JA; Vollmer RR; Cai HM; Miedlar JA; Rinaman L. 2005. Enhanced initial and sustained intake of sucrose solution in mice with an oxytocin gene deletion. Am J Physiol Regul Integr Comp Physiol 289(6):R1798-806. [PubMed: 16150836] [MGI Ref ID J:102577]
Assinder SJ; Rezvani A; Nicholson HD. 2002. Oxytocin promotes spermiation and sperm transfer in the mouse. Int J Androl 25(1):19-27. [PubMed: 11869373] [MGI Ref ID J:103024]
Bernatova I; Rigatto KV; Key MP; Morris M. 2004. Stress-induced pressor and corticosterone responses in oxytocin-deficient mice. Exp Physiol 89(5):549-57. [PubMed: 15184356] [MGI Ref ID J:105540]
Billings LB; Spero JA; Vollmer RR; Amico JA. 2006. Oxytocin null mice ingest enhanced amounts of sweet solutions during light and dark cycles and during repeated shaker stress. Behav Brain Res 171(1):134-41. [PubMed: 16677726] [MGI Ref ID J:108978]
Crawley JN; Chen T; Puri A; Washburn R; Sullivan TL; Hill JM; Young NB; Nadler JJ; Moy SS; Young LJ; Caldwell HK; Young WS. 2007. Social approach behaviors in oxytocin knockout mice: comparison of two independent lines tested in different laboratory environments. Neuropeptides 41(3):145-63. [PubMed: 17420046] [MGI Ref ID J:124563]
DeVries AC; Young WS 3rd; Nelson RJ. 1997. Reduced aggressive behaviour in mice with targeted disruption of the oxytocin gene. J Neuroendocrinol 9(5):363-8. [PubMed: 9181490] [MGI Ref ID J:41146]
Macbeth AH; Lee HJ; Edds J; Young WS rd. 2009. Oxytocin and the oxytocin receptor underlie intrastrain, but not interstrain, social recognition. Genes Brain Behav 8(5):558-67. [PubMed: 19531157] [MGI Ref ID J:151090]
Mantella RC; Vollmer RR; Amico JA. 2005. Corticosterone release is heightened in food or water deprived oxytocin deficient male mice. Brain Res 1058(1-2):56-61. [PubMed: 16168966] [MGI Ref ID J:101830]
Mantella RC; Vollmer RR; Li X; Amico JA. 2003. Female oxytocin-deficient mice display enhanced anxiety-related behavior. Endocrinology 144(6):2291-6. [PubMed: 12746288] [MGI Ref ID J:83709]
Michelini LC; Marcelo MC; Amico J; Morris M. 2003. Oxytocinergic regulation of cardiovascular function: studies in oxytocin-deficient mice. Am J Physiol Heart Circ Physiol 284(6):H2269-76. [PubMed: 12531722] [MGI Ref ID J:83910]
Miedlar JA; Rinaman L; Vollmer RR; Amico JA. 2007. Oxytocin gene deletion mice overconsume palatable sucrose solution but not palatable lipid emulsions. Am J Physiol Regul Integr Comp Physiol 293(3):R1063-8. [PubMed: 17596329] [MGI Ref ID J:124698]
Pedersen CA; Vadlamudi SV; Boccia ML; Amico JA. 2006. Maternal behavior deficits in nulliparous oxytocin knockout mice. Genes Brain Behav 5(3):274-81. [PubMed: 16594980] [MGI Ref ID J:122235]
Puryear R; Rigatto KV; Amico JA; Morris M. 2001. Enhanced salt intake in oxytocin deficient mice. Exp Neurol 171(2):323-8. [PubMed: 11573985] [MGI Ref ID J:72051]
Rigatto K; Puryear R; Bernatova I; Morris M. 2003. Salt appetite and the renin-angiotensin system: effect of oxytocin deficiency. Hypertension 42(4):793-7. [PubMed: 12953013] [MGI Ref ID J:103065]
Rinaman L; Vollmer RR; Karam J; Phillips D; Li X; Amico JA. 2005. Dehydration anorexia is attenuated in oxytocin-deficient mice. Am J Physiol Regul Integr Comp Physiol 288(6):R1791-9. [PubMed: 15718385] [MGI Ref ID J:98510]
Sclafani A; Rinaman L; Vollmer RR; Amico JA. 2007. Oxytocin knockout mice demonstrate enhanced intake of sweet and nonsweet carbohydrate solutions. Am J Physiol Regul Integr Comp Physiol 292(5):R1828-33. [PubMed: 17272659] [MGI Ref ID J:121469]
Vollmer RR; Li X; Karam JR; Amico JA. 2006. Sodium ingestion in oxytocin knockout mice. Exp Neurol 202(2):441-8. [PubMed: 16930592] [MGI Ref ID J:144672]
Wersinger SR; Temple JL; Caldwell HK; Young WS rd. 2008. Inactivation of the oxytocin and the vasopressin (Avp) 1b receptor genes, but not the Avp 1a receptor gene, differentially impairs the Bruce effect in laboratory mice (Mus musculus). Endocrinology 149(1):116-21. [PubMed: 17947352] [MGI Ref ID J:141469]
Wintermantel TM; Mayer AK; Schutz G; Greiner EF. 2002. Targeting mammary epithelial cells using a bacterial artificial chromosome. Genesis 33(3):125-30. [PubMed: 12124945] [MGI Ref ID J:95736]
Young WS 3rd; Shepard E; DeVries AC; Zimmer A; LaMarca ME; Ginns EI; Amico J; Nelson RJ; Hennighausen L; Wagner KU. 1998. Targeted reduction of oxytocin expression provides insights into its physiological roles. Adv Exp Med Biol 449:231-40. [PubMed: 10026810] [MGI Ref ID J:91657]
Colony Maintenance
Breeding & Husbandry This strain is maintained by heterozygous sibling matings. Expected coat color from breeding:Black,White Bellied Agouti Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 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.
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 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 for further information. |
|---|---|
| Supply Notes |
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| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 101045 B6129SF2/J | (approximate) | |
| 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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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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