Overview

These beta3-mutant mice lack the beta3 coding region of the Gabrb3 (gamma-aminobutyric acid (GABA-A) receptor, subunit beta 3) locus and may be useful in studying neurodevelopmental disorders such as cleft palate, seizures, epilepsy, and sensitivity to anesthetics and ethanol. In addition, the observed behavioral deficits (especially regarding social behaviors) indicate that mutant mice may be a useful model of autism spectrum disorders.

Of note, several strains bearing gamma-aminobutyric acid (GABA-A) receptor mutations are available from this donating investigator (Dr. Gregg Homanics, University of Pittsburgh), including Gabra1 (Stock No. 004318), Gabra4 (Stock No. 006874), Gabra6 (Stock No. 002710), Gabrb3 (Stock No. 002711), Gabrd (Stock No. 003725), and Gabrg2 (Stock No. 003137).

Donating Investigator

Gregg E Homanics, University of Pittsburgh

Genetic overview

Genetic Background	Generation

Gabrb3^tm1Geh

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Gabrb3	gamma-aminobutyric acid (GABA) A receptor, subunit beta 3

View Genetics

Research Applications

Neurobiology Research
Developmental Biology Research
Cell Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The gamma-Aminobutyric acid type A receptors mediate the majority of rapid inhibitory synaptic transmission in the CNS. The beta3 subunit is an essential component of these receptors in many brain regions, especially during development, and is implicated in several pathophysiologic processes. The majority of mice homozygous for the Gabrb3^tm1Geh mutation (or beta3-/-) die at birth with ~60% displaying cleft palate and the remaining ~35% die for unidentified reasons. Homozygous females that survive are fertile but do not care for their pups. Survivors have frequent myoclonus and occasional epileptic seizures, are hypersensitive to external stimuli and handling, have a lack of coordination and display altered responses to certain anesthesias. In addition, the observed behavioral deficits (especially regarding social behaviors) indicate that mutant mice may be a useful model of autism spectrum disorders.

Of note, several strains bearing gamma-aminobutyric acid (GABA-A) receptor mutations are available from this donating investigator (Dr. Gregg Homanics, University of Pittsburgh), including Gabra1 (Stock No. 004318), Gabra4 (Stock No. 006874), Gabra6 (Stock No. 002710), Gabrb3 (Stock No. 002711), Gabrd (Stock No. 003725), and Gabrg2 (Stock No. 003137).

Development

This strain was developed in the laboratory of Dr. Gregg Homanics at the University of Pittsburgh. The vector containing Pgk-neo was inserted by homologous recombination and resulted in deletion of the promoter and exons 1 and 2 of the Gabrb3 gene. The 129X1/SvJ x 129S1/Sv-derived R1 ES cell line was used.

Control Suggestions

Wild-type from the colony

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Delorey TM; Sahbaie P; Hashemi E; Homanics GE; Clark JD. 2008. Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: A potential model of autism spectrum disorder. Behav Brain Res 187(2):207-20PubMed: 17983671 MGI: J:130259
Homanics GE; DeLorey TM; Firestone LL; Quinlan JJ; Handforth A ; Harrison NL ; Krasowski MD ; Rick CE ; Korpi ER ; Makela R ; Brilliant MH ; Hagiwara N ; Ferguson C ; Snyder K ; Olsen RW. 1997. Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior. Proc Natl Acad Sci U S A 94(8):4143-8PubMed: 9108119 MGI: J:39801

View All References

Genetics

Gabrb3^tm1Geh

Allele Symbol: Gabrb3^tm1Geh

Allele Name	targeted mutation 1, Gregg E Homanics
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	beta3-
Gene Symbol and Name	Gabrb3, gamma-aminobutyric acid (GABA) A receptor, subunit beta 3
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	7
Molecular Note	A neomycin resistance cassette replaced 2.8 kb of sequence, including exons 1-3.
Mutations Made By	Gregg Homanics, University of Pittsburgh

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

autism spectrum disorder

Research Areas By Phenotype

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

Neurobiology Research
- Receptor Defects
  - GABA receptor
- Neurodevelopmental Defects
  - Autism
- Epilepsy

Genotype: Gabrb3^tm1Geh related

Developmental Biology Research
- Neurodevelopmental Defects
Neurobiology Research
- Behavioral and Learning Defects
- Epilepsy
- Neurodevelopmental Defects
- Neurotransmitter Receptor and Synaptic Vesicle Defects
- Receptor Defects
- Channel and Transporter Defects
  - chloride: GABAA receptor
  - chloride
Cell Biology Research
- Channel and Transporter Defects
  - chloride
  - chloride: GABAA receptor

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Gabrb3^tm1Geh/Gabrb3^tm1Geh
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

behavior/neurological phenotype

abnormal behavior
- frequently seen sleeping away from nesting material

abnormal nest building behavior
- at 1, 24 and 48 hours after introduction of new nestlet material, mice utilize significantly less material than wild-type controls
- location of nest construction is different
- significant impairment in their ability to achieve the nest complexity exhibited by the controls

abnormal response to novel object
- decreased amount of time spent investigating a novel object compared to wild-type
- increased time until first contact with a novel object compared to wild-type

abnormal social/conspecific interaction
- fail to show a significant preference for spending time in the interaction chamber adjacent to the stimulus cage containing an unfamiliar mouse as opposed to spending time in the interaction chamber adjacent to an empty stimulus cage
- mice fail to exhibit a preference for interacting with a new mouse over a familiar mouse

circling

decreased vertical activity
- the mean duration of each rearing event is decreased compared to controls
- total number of rearings differs from wild-type littermates and C57BL/6J mice but not from 129X1/SvJ mice

hyperactivity
- a higher degree of ambulatory activity than control mice
- a higher number of entries, in regards to the total transitions between all chambers, of a social interaction apparatus

nervous system phenotype

abnormal cerebellum vermis lobule II morphology
- significant decrease in the surface area

abnormal cerebellum vermis lobule III morphology
- significant decrease in the surface area

abnormal cerebellum vermis lobule IV morphology
- significant decrease in the surface area

abnormal cerebellum vermis lobule morphology

abnormal cerebellum vermis lobule V morphology
- significant decrease in the surface area

abnormal cerebellum vermis lobule VI morphology
- significant decrease in the surface area

abnormal cerebellum vermis lobule VII morphology
- significant decrease in the surface area

Genotype: Gabrb3^tm1Geh/Gabrb3^tm1Geh
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

abnormal motor capabilities/coordination/movement

abnormal parental behavior
- failure to nuture offspring

circling
- many have been observed to run continuously in tight circles for extended periods of time

hyperactivity

hyperresponsive
- hyperresponsive to human contact and other sensory stimuli

impaired coordination
- have difficulty walking on grids and repeatedly fall off platforms and rotarods

impaired swimming
- have difficulty swimming

limb grasping

seizures
- variable severity of epileptic seizures in mice over 10 weeks of age

craniofacial phenotype

cleft palate
- about 57% exhibit cleft palate

digestive/alimentary phenotype

cleft palate
- about 57% exhibit cleft palate

growth/size/body region phenotype

cleft palate
- about 57% exhibit cleft palate

decreased body size
- 5-10% that survive to adulthood are runted until weaning but achieve normal body weight by adulthood

hearing/vestibular/ear phenotype

abnormal auditory brainstem response waveform shape
- at 6 weeks, suprathreshold ABR amplitudes in homozygotes are significantly reduced in amplitude, by at least 50% at all test frequencies and sound levels

abnormal cochlea morphology
- at >24 weeks, homozygotes exhibit basal-turn histopathology
- rarity and fragility of homozygotes prevented evaluation of cochlear histopathology at 6 weeks, as none were killed at this age

abnormal cochlear IHC afferent innervation pattern
- at >24 weeks, homozygotes display a significant reduction in the density of IHC afferent innervation relative to age-matched wild-type mice, indicating neuropathy

abnormal cochlear OHC efferent innervation pattern
- at >24 weeks, homozygotes display a reduction in OHC efferent innervation, with fewer efferent axons crossing to OHCs at the level of the tunnel of Corti relative to age-matched wild-type mice

abnormal distortion product otoacoustic emission
- at 16 kHz (middle cochlear region), ABR shifts are similar in magnitude to the observed DPOAE shifts, suggesting that the threshold shift arises at, or before, the stage of OHC transduction and amplification
- at 6 weeks, homozygotes display significantly elevated DPOAE thresholds across all test frequencies relative to wild-type mice, with DPOAE thresholds of >60 dB at high frequencies

cochlear inner hair cell degeneration
- at ~24 weeks, homozygotes display a nearly complete loss of IHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map

cochlear outer hair cell degeneration
- at ~24 weeks, homozygotes display a nearly complete loss of OHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map

increased or absent threshold for auditory brainstem response
- ABR threshold elevation corresponds to >2 orders of magnitude of stimulus amplitude
- at 6 weeks, homozygotes display severe cochlear dysfunction, as shown by highly significant ABR threshold elevations of 20-45 dB across a range of test frequencies, with peak loss occurring at 22.6 kHz

sensorineural hearing loss

type IV spiral ligament fibrocyte degeneration
- at >24 weeks, homozygotes display widespread loss of type IV fibrocytes, spreading farther apically

mortality/aging

perinatal lethality, incomplete penetrance
- 30% with normal palates die neonatally
- 90% die within 1 day of birth

premature death
- animals surviving to birth live an average of 18 weeks

nervous system phenotype

abnormal CNS synaptic transmission
- 80% decrease in the maximal amplitude of GABA-activated chloride currents in dorsal root ganglion

abnormal cochlear IHC afferent innervation pattern
- at >24 weeks, homozygotes display a significant reduction in the density of IHC afferent innervation relative to age-matched wild-type mice, indicating neuropathy

abnormal cochlear nerve morphology
- at >24 weeks, homozygotes display clear signs of cochlear nerve abnormalities (progressive loss of afferent terminals)

abnormal cochlear OHC efferent innervation pattern
- at >24 weeks, homozygotes display a reduction in OHC efferent innervation, with fewer efferent axons crossing to OHCs at the level of the tunnel of Corti relative to age-matched wild-type mice

cochlear ganglion degeneration
- at >24 weeks, homozygotes show partial loss of spiral ganglion cells but only in cochlear regions in which IHCs are degenerated

cochlear ganglion hypoplasia
- adult homozygotes show hypoplasia of spiral ganglion cells in the middle and basal turns of the cochlea, while the apical turn remains unaffected
- spiral ganglion cell hypoplasia is strictly due to a size reduction of calretinin-negative ganglion cells

cochlear inner hair cell degeneration
- at ~24 weeks, homozygotes display a nearly complete loss of IHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map

cochlear outer hair cell degeneration
- at ~24 weeks, homozygotes display a nearly complete loss of OHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map

seizures
- variable severity of epileptic seizures in mice over 10 weeks of age

small cochlear ganglion
- adult homozygotes display significantly smaller cochlear ganglion cell areas at every sampled region in the spiral ganglion, except the apical cochlear turn
- Normal - in contrast, mutant calretinin-positive ganglion cells are of normal size and proportion relative to wild-type cells
- mutant calretinin-negative cells are smaller at each sampled location in the spiral ganglion relative to wild-type cells
- the reduction in mean somatic area of mutant calretinin-negative cells is 5.2% in the basal turn, 8.7% in the middle turn, and 12.2% in the apical turn of the spiral ganglion relative to wild-type cells

small vestibular ganglion
- adult homozygotes display significantly smaller ganglion cell areas in both divisions of Scarpa's ganglion (superior and inferior) relative to wild-type mice
- Normal - in contrast, mutant calretinin-positive ganglion cells are of normal size and proportion relative to wild-type cells
- mutant calretinin-negative cells are smaller in both divisions of Scarpa's ganglion relative to wild-type cells
- the reduction in mean somatic area of mutant calretinin-negative cells is 9.5% in the inferior division and 21.5% in the superior division of Scarpa's ganglion

vestibular ganglion hypoplasia
- adult homozygotes show ganglion cell hypoplasia in both divisions of Scarpa's ganglion
- Scarpa ganglion cell hypoplasia is strictly due to a size reduction of calretinin-negative ganglion cells

skeleton phenotype

type IV spiral ligament fibrocyte degeneration
- at >24 weeks, homozygotes display widespread loss of type IV fibrocytes, spreading farther apically

References

Delorey TM; Sahbaie P; Hashemi E; Homanics GE; Clark JD. 2008. Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: A potential model of autism spectrum disorder. Behav Brain Res 187(2):207-20PubMed: 17983671 MGI: J:130259
Homanics GE; DeLorey TM; Firestone LL; Quinlan JJ; Handforth A ; Harrison NL ; Krasowski MD ; Rick CE ; Korpi ER ; Makela R ; Brilliant MH ; Hagiwara N ; Ferguson C ; Snyder K ; Olsen RW. 1997. Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior. Proc Natl Acad Sci U S A 94(8):4143-8PubMed: 9108119 MGI: J:39801

Additional References

Dellovade TL; Davis AM; Ferguson C; Sieghart W; Homanics GE; Tobet SA. 2001. GABA influences the development of the ventromedial nucleus of the hypothalamus. J Neurobiol 49(4):264-76PubMed: 11745664 MGI: J:79217

Additional - Gabrb3^tm1Geh related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Gabrb3
- Genotyping resources and troubleshooting
Breeding Considerations

This strain is currently maintained on a mixed C57BL/6J x 129 genetic background. It is maintained by mating heterozygous mice to normal wildtype siblings.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129-Gabrb3^tm1Geh/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #002711 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Gabrb3<tm1Geh>

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Gabrb3tm1Geh

Allele Symbol: Gabrb3tm1Geh

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: Gabrb3tm1Geh related

Mammalian Phenotype Terms by Genotype

Genotype: Gabrb3tm1Geh/Gabrb3tm1Gehinvolves: 129S1/Sv * 129X1/SvJ * C57BL/6J

behavior/neurological phenotype

nervous system phenotype

Genotype: Gabrb3tm1Geh/Gabrb3tm1Gehinvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

craniofacial phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

mortality/aging

nervous system phenotype

skeleton phenotype

References

Additional References

Additional - Gabrb3tm1Geh related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Gabrb3^tm1Geh

Allele Symbol: Gabrb3^tm1Geh

Genotype: Gabrb3^tm1Geh related

Genotype: Gabrb3^tm1Geh/Gabrb3^tm1Geh
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Genotype: Gabrb3^tm1Geh/Gabrb3^tm1Geh
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Additional - Gabrb3^tm1Geh related