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Recombinant interleukin 6 

Inducer Abbreviation: rIL-6
Model Subtype: Biological
Model Species:Mus musculus
Statistics Box:
No of Reports: 4
No of Models: 6




Model Summary

A model to experimentally show that prenatal immune activation is an environmental risk factor for adult ventricular enlargement, works similar to poly(I:C) treament of mother at E12.5.

Human Clinical Evidence et al.


Strong epidemiological evidence suggests that maternal infection during prenatal life may contribute to an increased risk of schizophrenia or autism in offspring

Exposure

Prenatal exposure from mother

Mode of Action

Interleukin 6 is shown to be very important in the induction of ASD related phenotype in offspring exposed to maternal immune activation, via poly(I:C) treatment of mother

Usage

Immunostimulant

References

Type
Title
Author, Year
Primary
Maternal immune activation alters fetal brain development through interleukin-6.
Additional
The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring.
Additional
Effects of maternal immune activation on gene expression patterns in the fetal brain.
Additional
Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism.

M_RIL6_1_IN_B

Construct Definition: Administration of carrier-free mouse recombinant interleukin-6 (rIL-6) on E12.5.
Administration Dose: 5 microg
Administration Route: Intraperitoneal (i.p.)
Administration Age:
Strain of Origin: C57BL/6J
Model Source: Jackson Laboratory

M_RIL6_2_IN_B

Construct Definition: Administration of carrier-free mouse recombinant interleukin-6 (rIL-6) on E12.5, the authors note that C57BL/6 mice used were of a stable immunological phenotype as they used these mice to study cytokine levels, therefore these are probably a substrain sold by Taconic.
Administration Dose: 10 microg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: C57BL/6J
Model Source: Taconic, USA

M_RIL6_3_IN_B

Construct Definition: Intraventricular injection, into the third ventricle of the fetal brain, of mouse recombinant, carrier-free IL-6 (R&D), 0.6 L of 10ng/L.
Administration Dose: 6 ng
Administration Route: Intraventricular
Administration Age: E14.5
Strain of Origin: C57BL/6J
Model Source: Taconic, USA

M_RIL6_4_IN_B

Construct Definition: Pregnant C57BL/6J females were administered i.p. injections of 30 microgram/kg recombinant interleukin-6 (rIL-6) daily between E12.5 and E16.5.
Administration Dose: 30 microg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5-E16.5
Strain of Origin: C57BL/6J
Model Source: Charles River

M_RIL6_1_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Sensorimotor gating 1
  Decreased
Description:  Lower prepulse inhibition, compared to offspring from saline-injected dams
Exp Paradigm:  Prepulse inhibition
  Prepulse inhibition
  Adult
  Tissue weight 2
  Decreased
Description:  Decreased placental weight
Exp Paradigm:  Placental weight measurements
  Measurement of placental weight
  Unreported
  Cued or contextual fear conditioning: latent inhibition 1
  Decreased
Description:  Lack of significant latent inhibition (increased freezing response), compared to offspring from saline-injected dams
Exp Paradigm:  fear conditioning test: latent inhibition
  Fear conditioning test
  Adult
  Gene expression 2
  Abnormal
Description:  Abnormal transcriptome profile indicated by 195 genes differentially expressed in embryonic brain 3 h after injection
Exp Paradigm:  Gene Expression
  Gene expression microarray
  E12.5
  Gene expression 2
  Increased
Description:  Increased gene expression of crystallin gene family: cryaa, cryba1, cryba2, cryba4, crybb1, crybb3, cryga and crygb/crygc in embryonic brain 3 h after injection
Exp Paradigm:  Gene Expression
  Gene expression microarray
  E12.5
Gene expression2
 No change
 Quantitative pcr (qrt-pcr)
 6 months
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

M_RIL6_2_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Cortical lamination 1
  Decreased
Description:  Cortical cytoarchitecture is disorganized, with 'intrusions' and 'protrusions', in offspring of mothers treated with rIL-6 at E12.5(similar to MIA via poly(I:C)), detected using markers: SATB2 (a marker for postmitotic neurons), TBR1(marker for deep cortical layers) and CTIP2 show disorganized expression
  Immunohistochemistry
  E18.5
  Ultrasonic vocalization: isolation induced 1
  Increased
Description:  rIL-6 treatment of mothers at E12.5 results in increased USV calls by pups, similar to poly(I:C) treatment for maternal immune activation
Exp Paradigm:  Monitoring ultrasonic vocalizations: manual count
 
 
  Cytokine levels: pro-inflammatory 1
  Increased
Description:  rIL-6 treatment of mothers at E12.5 results in increased levels of IL-17a (pro-inflammatory cytokine) by E14.5 in the sera of mothers, similar to poly(I:C) treatment for maternal immune activation
  Elisa
  E14.5
 Not Reported: Circadian sleep/wake cycle ,   Developmental profile ,   Emotion ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

M_RIL6_3_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Ultrasonic vocalization: isolation induced1
 No change
 Monitoring ultrasonic vocalizations
 P7-P9
Cortical lamination1
 No change
 Immunohistochemistry
 E18.5
 Not Reported: Circadian sleep/wake cycle ,   Developmental profile ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

M_RIL6_4_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Neuroreceptor levels: oxt 1
  Increased
Description:  MIA exposed adult male mice show increase in oxytocin receptor in the cingulate cortex region 1 including the anterior cingulate cortex compared with controls but no change of oxytocin receptor density was seen in the prelimbic cortex, anterior olfactory nucleus, nucleus accumbens, lateral septal nucleus, bed nucleus of the stria terminalis, ventral reuniens, paraventricular, and ventromedial hypothalamic nucleus.
Exp Paradigm:  Anterior cingulate cortex, prelimbic cortex, anterior olfactory nucleus, nucleus accumbens, lateral septal nucleus, bed nucleus of the stria terminalis, ventral reuniens, paraventricular, and ventromedial hypothalamic nucleus
  Autoradiographic analysis
  Adult
  Self grooming: perseveration 1
  Increased
Description:  MIA exposed adult male mice show increased grooming when placed in a beaker compared with controls.
  Grooming behavior assessments
  Adult
  Social memory 1
  Decreased
Description:  MIA exposed adult male mice show decrease in social novelty index compared with controls.
  Three-chamber social approach test
  Adult
  Social approach 1
  Decreased
Description:  MIA exposed adult male mice show decrease in sociability index compared with controls.
  Three-chamber social approach test
  Adult
  Ultrasonic vocalization: interaction induced: opposite sex stimulus 1
  Decreased
Description:  MIA exposed adult male mice show decrease in ultrasonic vocalization evoked by the presence of a C57 estrus female mouse compared with controls.
  Monitoring ultrasonic vocalizations
  Adult
Repetitive digging1
 No change
 Marble burying test
 Adult
 Not Reported: Circadian sleep/wake cycle ,   Developmental profile ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neurophysiology ,   Physiological parameters ,   Seizure ,   Sensory ,  
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