Phenotypes associated with this allele

• Allele Symbol: Gabrg2^tm1Wul
• Allele Name: targeted mutation 1, Peter Wulff
• Allele ID: MGI:3721943
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gabrg2^tm1Wul/Gabrg2^tm1Wul Tg(Pcp2-cre)2Mpin/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3723058
cn2	Gabrg2^tm1Wul/Gabrg2^tm1Wul Tg(Pcp2-cre)2Mpin/? Tg(Pcp2-EGFP/Gabrg2)1Wul/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:3757963
cn3	Gabrg2^tm1Wul/Gabrg2^tm1Wul Hdc^tm1.1(icre)Wwis/Hdc^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5461821

Genotype
MGI:3723058

cn1

• Allelic Composition: Gabrg2^tm1Wul/Gabrg2^tm1Wul; Tg(Pcp2-cre)2Mpin/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

behavior/neurological phenotype ( J:124171 )

N • mice have no motor disabilities, no ataxia or tremor and performed normally on a rotarod test

impaired behavioral response to xenobiotic ( J:124171 )

• mice are resistant to zolpidem induced sedative and ataxic effects

nervous system

abnormal inhibitory postsynaptic currents ( J:124171 )

• miniature inhibitory postsynaptic currents are absent from all Purkinje cells

Genotype
MGI:3757963

cn2

• Allelic Composition: Gabrg2^tm1Wul/Gabrg2^tm1Wul; Tg(Pcp2-cre)2Mpin/?; Tg(Pcp2-EGFP/Gabrg2)1Wul/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

behavior/neurological

impaired behavioral response to xenobiotic ( J:124171 )

• treatment with zolpiderm does not produce sedation or overt ataxia

• sensitivity to zolpidem is only restored in Purkinje cells

impaired coordination ( J:124171 )

• following treatment with 3 mg/kg of zolpidem, mice exhibit reduced ability to stay on a rotating rod

• following treatment with zolpidem, mice need more time to cross a hanging beam than do untreated mice

• however, untreated mice have no motor disabilities, no ataxia or tremor and performed normally on a rotarod test and pre-treatment with flumazenil blocks the effects of zolpiderm

nervous system

abnormal inhibitory postsynaptic currents ( J:124171 )

• mice treated with zolpidem exhibit a raise the amplitude and increase the charge of miniature inhibitory postsynaptic currents (mIPSCs) indicating a restoration of zolpiderm-sensitivity but only in Purkinje cells

• due to mosaic expression of the transgene in female mice with integration into the X chromosome, some mice exhibit a lack of mIPSCsdue to mosaic expression of the transgene in female mice with integration into the X chromosome, some mice exhibit a lack of mIPSCs

• however, in GFP+ cells normal zolpidem-sensitivity is restored

Genotype
MGI:5461821

cn3

• Allelic Composition: Gabrg2^tm1Wul/Gabrg2^tm1Wul; Hdc^{tm1.1(icre)Wwis}/Hdc⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system

abnormal neuron physiology ( J:188103 )

• tuberomammillary nucleus (TMN) neurons lacking GABAA receptors are more excitable than control neurons; more action potentials (APs) are produced for a given current injection and current needed to reach threshold for AP generation is reduced significantly

• tuberomammillary nucleus neurons have increased membrane time constants compared to control neurons

abnormal GABA-mediated receptor currents ( J:188103 )

• whole cell voltage-clamped mutant neurons in the ventral tuberomammillary (VTM) nucleus lack fast GABAA receptor-mediated IPSCs, but are IPSCs are observed in controls

• in dorsal lateral geniculate (DLG) nucleus slice preparations, only 30% of neurons exhibit GABAergic IPSCs compared to most neurons tested in control slices

abnormal inhibitory postsynaptic currents ( J:188103 )

behavior/neurological

behavior/neurological phenotype ( J:188103 )

N • mice appear indistinguishable from controls in health, behavior and appearance

N • total sleep-wake time, EEG power spectrum, and duration of REM and non-REM (NREM) periods during the 24 hour cycle do not differ from controls

N • habituation to a new environment is not different from controls

N • propofol-induced loss of righting reflex (LORR) is not different from controls