Phenotypes associated with this allele

• Allele Symbol: Gabrd^tm1Geh
• Allele Name: targeted mutation 1, Gregg E Homanics
• Allele ID: MGI:1861926
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gabrd^tm1Geh/Gabrd^tm1Geh	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3713529
hm2	Gabrd^tm1Geh/Gabrd^tm1Geh	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3639693

Genotype
MGI:3713529

hm1

• Allelic Composition: Gabrd^tm1Geh/Gabrd^tm1Geh
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

behavior/neurological

abnormal depression-related behavior ( J:145475 )

• 18 day postpartum mice exhibit decreased preference for sucrose (anhedonia) compared to virgin mice or postpartum wild-type mice

behavioral despair ( J:145475 )

• 18 day postpartum mice exhibit decreased latency to immobility and increased immobility time in a forced swim test compared to virgin mice and postpartum wild-type mice

increased anxiety-related response ( J:145475 )

• in a resident-intruder assay, postpartum mice exhibit increased digging, burrowing, and circling compared to virgin mice or postpartum wild-type mice without an increase in aggressive behavior

abnormal maternal nurturing ( J:145475 )

♀ • more pups, regardless of genotype, die of maternal neglect or pup cannibalism than in litters nurtured by wild-type mice

♀ • however, treatment with THIP (a GABA A receptor delta subunit agonist) improves pup survival

abnormal pup retrieval ( J:145475 )

♀ • postpartum female mice allow pups to disperse more than postpartum wild-type mice

pup cannibalization ( J:145475 )

♀

abnormal nest building behavior ( J:145475 )

• postpartum mice fail to build a proper nest unlike postpartum wild-type mice

nervous system

abnormal nervous system electrophysiology ( J:145475 )

• virgin and 18 day postpartum mice exhibit decreased tonic inhibition in dentate gyrus granule cells compared to virgin and postpartum wild-type mice

• however, mean conductance of synaptic GABA receptors is normal

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:112951 )

N • at 6 weeks of age, homozygotes show no signs of cochlear pathology, with normal hearing sensitivity, as determined by ABR/DPOAE assays across various test frequencies, and normal OHC efferent function, as assessed by measuring DPOAE suppression caused by efferent-bundle shocks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
postpartum depression		DOID:9478		J:145475

Genotype
MGI:3639693

hm2

• Allelic Composition: Gabrd^tm1Geh/Gabrd^tm1Geh
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

mortality/aging

postnatal lethality ( J:64288 )

• only 20.5% of pups weaned are homozygous for the mutation, indicating that ~5% of homozygotes die prior to weaning

behavior/neurological

impaired behavioral response to anesthetic ( J:64288 )

• Gabrd-deficient mice show a 54% and 38% reduction in sleep time duration to alphaxalone at 8 mg/kg and 16 mg/kg respectively compared to controls

• an injection of 8 mg/kg of pregnanolone results in a 42% reduction in sleep time in mutants compared to controls

abnormal contextual conditioning behavior ( J:110073 )

• percent freezing of female Gabrd-deficient mice is significantly greater than that of wild-type during the tone test in a context conditioning paradigm 24 hours after the cued conditioning

abnormal cued conditioning behavior ( J:110073 )

• percent freezing of female Gabrd-deficient mice is significantly greater than that of wild-type during trace conditioning

decreased anxiety-related response ( J:64288 )

• mutants display fewer open arm entries in the elevated plus maze; injection of ganaxolone to wild-type mice resulted in a 2-fold increase in open arm entries but had no effect on mutants

absence seizures ( J:64288 )

• ganaxolone failed to prolong PTZ-induced absence-like seizures in null mice but increased freezing 74% in controls

nervous system

absence seizures ( J:64288 )

• ganaxolone failed to prolong PTZ-induced absence-like seizures in null mice but increased freezing 74% in controls

abnormal inhibitory postsynaptic currents ( J:64288 )

• decay time of mini IPSCs is faster in mutants than in wild-type controls

reproductive system

decreased litter size ( J:64288 )

• in the F3 generation, homozygous matings produced statistically fewer pups (6.3 pups/litter) than wild-type pairs (7.6 pups/litter)