OXT polymorphisms have been found to associate with a diagnosis of ASD (Chakrabarti et al., 2009; Francis et al., 2016), ASD subphenotypes (Yrigollen et al., 2008; Francis et al., 2016), and autistic-like traits in the general population (Hovey et al., 2014).
Molecular Function
This gene encodes a precursor protein that is processed to produce oxytocin and neurophysin I. Oxytocin is a hormone involved in a number of processses, including contraction of smooth muscle during parturition and lactation, cognition, tolerance, adaptation, complex sexual and maternal behaviour, and the regulation of water excretion and cardiovascular functions.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Arginine vasopressin and oxytocin modulate human social behavior.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
An oxytocin targeting vector constructed to delete exon1 of the oxytocin was injected in ES cells (Nishimore et al, PNAS, 1996). Chimaeric males (generated from mutant 129S7/SvEvBrd-Hprtb-m2 embryonic stem cells) were mated to C57BL/6J females to generate Oxt null mice. Since Oxt null mothers do not lactate, pups were cross-fostered to Oxt WT mothers within 2 h of birth to provide comparable postnatal experience for both mutant and control litter types.
Allele Type: Homozygous
Strain of Origin: 129S7/SvEvBrd-Hprtb-m2 and C57BL/6J
Genetic Background: 129S7/SvEvBrd-Hprtb-m2 and C57BL/6J
ES Cell Line: Hprt-negative AB2.1 ES cells
Mutant ES Cell Line: Mutant 129S7/SvEvBrd-Hprtb-m2 embryonic stem cells
Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
OXT null mice used in these studies were derived from the line developed by Young et al 1996 where the 2nd and 3rd exons of the mouse OXT gene were deleted using homologous recombination.
Allele Type: Homozygous
Strain of Origin: C57BL/6 strain and 129
Genetic Background: C57BL/6 strain and 129
ES Cell Line: Mutant ES Cell Line: 129
Model Source:
Model Type:
Genetic; Induced
Model Genotype:
Homozygous
Mutation:
Male OXTKO and WT control mice, F11 generation, are treated with CB1R antagonist AM251, 3mg/kg, i.p. CB1R antagonists decrease food intake presumably via interrupting central cannabinoid systems. AM251 is closely related in structure and activity to the CB1R antagonist SR141716, rimonabant, that was reported to enhance basal and post-stress plasma corticosterone concentrations when administered to mice in doses of 1 or 5 mg/kg (Patel et al., 2004).
Allele Type: Homozygous
Strain of Origin: C57BL/6 strain and 129
Genetic Background: C57BL/6 strain and 129
ES Cell Line: Mutant ES Cell Line: 129
Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Late pregnancy OxtKO mice and cycling wildtype controls to model pregnancy induced stress hyporesponsiveness.
Allele Type: Homozygous
Strain of Origin: C57BL/6 strain and 129
Genetic Background: C57BL/6 strain and 129
ES Cell Line: Mutant ES Cell Line: 129
Model Source:
Description: Oxt null mice showed no decline in the time spent investigating a male or an ovariectomized female indicating memory deficit where wt mice showed a characteristic decline in the time spent investigating a male or an ovariectomized female
Exp Paradigm: Males and females tested, repeated pairings with the same male or ovariectomized mouse,
Description: Oxt null mice showed no decline in the time spent investigating an ovariectomized female in repeated exposures, indicating memory deficit, where wt mice showed a characteristic decline in the time spent investigating a male or an ovariectomized female, over repeated exposures
Exp Paradigm: Males and females tested, repeated pairings with the same male or ovariectomized mouse,
Description: Oxt null mice spent less time investigating a lemon secented object than wt mice
Exp Paradigm: Mice were exposed to a lemon-scented object. operationally defined olfactory investigation as nasal contact with the tube holding the scent.
Description: Wt mice had a higher basal temperature than oxtko mice during the am251- and vehicle-treated phases of the study but the peak temperature achieved did not differ between genotype or treatment group
Exp Paradigm: Mice were studied at estimated day 1617 of pregnancy. after completion of the study, mice were sacrificed by co2 inhalation and the uterus dissected to verify pregnancy. a lubricated thermocouple temperature probe (omega, stanford, ct) was inserted to a uniform depth of 2.0 cm into the rectum of the mouse and maintained in place for 1015s. a temperature reading was recorded to the nearest 0.11. between 1000 and 1200 h, rectal temperature was recorded in mice of each genotype before and 10min after transfer to a metabolic cage.
Description: Treatment with am251 caused a significant decrease in the intake of intralipid in both wildtype and oxt ko genotypes. am251 also caused significant decreases in total calorie intake of similar magnitude in both genotypes. this indicates that the anorexigenic actions of the cb1 antagonist can occur independent of oxt-signalling pathways in mice.
Exp Paradigm: Measured effects of the cb1r antagonist am251 upon the intake of chow or a palatable lipid emulsion (4.1% intralipid solution). mice were maintained on powdered food, which allowed for accurate recording of food intake.
Description: The rise in core body temperature was not different between vehicle and am251 treatment in either wt or oxt ko genotype. because of the lower basal temperature in wt versus oxtko mice, the change in temperature was greater in wt than oxtko mice.
Exp Paradigm: Mice were studied at estimated day 1617 of pregnancy. after completion of the study, mice were sacrificed by co2 inhalation and the uterus dissected to verify pregnancy. a lubricated thermocouple temperature probe (omega, stanford, ct) was inserted to a uniform depth of 2.0 cm into the rectum of the mouse and maintained in place for 1015s. a temperature reading was recorded to the nearest 0.11. between 1000 and 1200 h, rectal temperature was recorded in mice of each genotype before and 10min after transfer to a metabolic cage.
Description: Late-pregnant mice confronted with the same stress as cycling control mice had comparable basal body temperatures but markedly blunted rises in core body temperature on exposure to stress
Exp Paradigm: Mice were studied at estimated day 1617 of pregnancy. after completion of the study, mice were sacrificed by co2 inhalation and the uterus dissected to verify pregnancy. a lubricated thermocouple temperature probe (omega, stanford, ct) was inserted to a uniform depth of 2.0 cm into the rectum of the mouse and maintained in place for 1015s. a temperature reading was recorded to the nearest 0.11. between 1000 and 1200 h, rectal temperature was recorded in mice of each genotype before and 10min after transfer to a metabolic cage.
