Phenotypes associated with this allele

• Allele Symbol: Gad2^tm2(cre)Zjh
• Allele Name: targeted mutation 2, Z Josh Huang
• Allele ID: MGI:4418713
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gad2^tm2(cre)Zjh/Gad2^tm2(cre)Zjh	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:4418723
cn2	Gad2^tm2(cre)Zjh/? Rai1^tm2.1Luo/Rai1^tm2.1Luo	either: (involves: 129S1/Sv * 129S4/SvJae * C57BL/6) or (involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6)	MGI:5817645
cn3	Dnm1^tm1Frk/Dnm1^+ Gad2^tm2(cre)Zjh/Gad2^+	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J * C57BL/6NTac * FVB/NJ	MGI:8260854
cn4	Gigyf1^em1Xio/Gigyf1^em1Xio Gad2^tm2(cre)Zjh/Gad2^+	involves: 129S4/SvJae * C57BL/6	MGI:7779934
cn5	Gabrd^tm1.1Jmag/Gabrd^+ Gad2^tm2(cre)Zjh/Gad2^+	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:5527106

Genotype
MGI:4418723

hm1

• Allelic Composition: Gad2^tm2(cre)Zjh/Gad2^tm2(cre)Zjh
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

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

normal phenotype

no abnormal phenotype detected ( J:151755 )

• mice are viable, fertile, normal in size and display no gross physical or behavioral abnormalities

Genotype
MGI:5817645

cn2

• Allelic Composition: Gad2^tm2(cre)Zjh/?; Rai1^tm2.1Luo/Rai1^tm2.1Luo
• Genetic Background: either: (involves: 129S1/Sv * 129S4/SvJae * C57BL/6) or (involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6)

behavior/neurological

abnormal associative learning ( J:237687 )

♂

impaired contextual conditioning behavior ( J:237687 )

♂ • decreased freezing behavior in contextual memory recall

impaired cued conditioning behavior ( J:237687 )

♂ • decreased freezing behavior in cued recall

Genotype
MGI:8260854

cn3

• Allelic Composition: Dnm1^tm1Frk/Dnm1⁺; Gad2^tm2(cre)Zjh/Gad2⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J * C57BL/6NTac * FVB/NJ

mortality/aging

postnatal lethality, incomplete penetrance ( J:373297 )

• mice show 100% lethal seizures starting as early as P12, fully penetrant by 3 weeks

• newborns administered a modest dose of an AAV9-based vector encoding a ubiquitously expressed, Dnm1-specific interfering RNA (RNAi) bivalently in tail-to-tail configuration with a neuron-specific, RNAi resistant, codon-optimized Dnm1 cDNA (RNAi and cDNA gene therapy) show prolonged survival with almost full growth recovery, however older RNAi and cDNA gene therapy treated mice exhibit aggression and females are not successful at raising their pups

growth/size/body

postnatal growth retardation ( J:373297 )

• mice show growth defects

• newborns administered a modest dose of the RNAi and cDNA gene therapy show prolonged survival with almost full growth recovery

behavior/neurological

seizures ( J:373297 )

• mice show 100% lethal seizures starting as early as P12, fully penetrant by 3 weeks

nervous system

seizures ( J:373297 )

• mice show 100% lethal seizures starting as early as P12, fully penetrant by 3 weeks

abnormal synaptic transmission ( J:373297 )

• the amplitude of evoked inhibitory responses onto excitatory neurons is decreased and the paired pulse ratio is increased, indicating an impairment in presynaptic GABA release

• however, amplitude and paired pulse ratios of evoked excitatory currents onto inhibitory neurons are unaltered

• the alterations in transmission from inhibitory to excitatory neurons are rectified by RNAi and cDNA gene therapy application

abnormal inhibitory postsynaptic currents ( J:373297 )

• although no change in the frequency of mIPSCs is seen, the size of IPSCs is increased in neurons and is reversed by tetrodotoxin treatment

increased paired-pulse ratio ( J:373297 )

• the paired pulse ratio of evoked inhibitory responses onto excitatory neurons is increased

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
developmental and epileptic encephalopathy 31A		DOID:0080437	OMIM:616346	J:373297

Genotype
MGI:7779934

cn4

• Allelic Composition: Gigyf1^em1Xio/Gigyf1^em1Xio; Gad2^tm2(cre)Zjh/Gad2⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

behavior/neurological

abnormal object recognition memory ( J:335507 )

♂ • mice exhibit an impairment in cognitive performance in the novel object recognition test

♂ • however, mice do not show changes in sociability, social novelty, rearing, marble burying, elevated plus maze, or T-maze

increased thigmotaxis ( J:335507 )

♂ • mice exhibit elevated anxiety levels, spending less time in centers of the open field

decreased grooming behavior ( J:335507 )

♂ • mice exhibit reduced grooming behavior

Genotype
MGI:5527106

cn5

• Allelic Composition: Gabrd^tm1.1Jmag/Gabrd⁺; Gad2^tm2(cre)Zjh/Gad2⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

nervous system

decreased susceptibility to pharmacologically induced seizures ( J:203336 )

• decreased seizure susceptibility in response 20mg/kg kainic acid as compared to controls

• decreased epilepitform activity over 120 min recording period

impaired ability to fire action potentials ( J:203336 )

• decreased average number of action potentials fired in CA1 pyramidal neurons in response to current injections above 40 pA

• decreased average number of action potentials fired in dentate gyrus granule cells in response to current injections above 60 pA

abnormal GABAergic neuron physiology ( J:203336 )

• decrease in tonic GABAergic currents recorded in interneurons from the molecular layer of the hippocampus as compared to controls

• decrease in tonic GABAergic currents recorded in interneurons from the stratum radiatum layer of the hippocampus as compared to controls

• increase in tonic GABAergic currents recorded in CA1 pyramidal neurons, however, no difference is observed in dentate gyrus granule cells as compared to controls

abnormal CNS synaptic transmission ( J:203336 )

• increase in spontaneous firing rate of stratum radiatum layer interneurons as compared to controls

• increase in firing rate of stratum radiatum layer interneurons in response to a single 1 s, 100 pA current injection as compared to controls

• increase in firing rate of molecular layer interneurons in response to a single 1 s, 100 pA current injection as compared to controls

• no differences are observed in resting potential or input resistance

increased excitatory postsynaptic current amplitude ( J:203336 )

• half maximal current amplitude (I₅₀) is increased in CA1 pyramidal neurons and dentate gyrus granule cells as compared to controls

abnormal inhibitory postsynaptic currents ( J:203336 )

• frequency of spontaneous IPSCs is increased in dentate gyrus granule cells (DGGCs) and CA1 pyramidal neurons

• peak amplitude of spontaneous IPSCs is increased in DGGCs and CA1 pyramidal neurons

• decrease in average inter-event interval (IEI) of spontaneous IPSCs

• increase in percentage of DGGCs and CA1 pyramidal cells following bursts of inhibitory postsynaptic currents as compared to control

behavior/neurological

decreased susceptibility to pharmacologically induced seizures ( J:203336 )

• decreased seizure susceptibility in response 20mg/kg kainic acid as compared to controls

• decreased epilepitform activity over 120 min recording period