Phenotypes associated with this allele

• Allele Symbol: Mapk8ip1^tm1Rjd
• Allele Name: targeted mutation 1, Roger J Davis
• Allele ID: MGI:2183313
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mapk8ip1^tm1Rjd/Mapk8ip1^tm1Rjd	involves: 129S6/SvEvTac * C57BL/6	MGI:3618376
cx2	Mapk8ip1^tm1Rjd/Mapk8ip1^tm1Rjd Mapk8ip2^tm1Rjd/Mapk8ip2^tm1Rjd	involves: 129S6/SvEvTac * 129X1/SvJ	MGI:4360031
cx3	Mapk8ip1^tm1Rjd/Mapk8ip1^tm1Rjd Mapk8ip2^tm1Rjd/Mapk8ip2^tm1Rjd	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6	MGI:3759994

Genotype
MGI:3618376

hm1

• Allelic Composition: Mapk8ip1^tm1Rjd/Mapk8ip1^tm1Rjd
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

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

nervous system

decreased susceptibility to neuronal excitotoxicity ( J:77616 )

• in vitro, mutant hippocampal neurons exhibit reduced stress-induced apoptosis following exposure to the excitotoxin kainate

• mutant neurons are also resistant to the apoptotic effects of anoxic stress induced by oxygen-glucose deprivation, as shown by reduced labeling in TUNEL assays and increased cell survival

• following exposure to kainite-induced excitotoxic stress, mutant hippocampal neurons display attenuated JNK activation despite a normal level of Jun protein expression

• in vivo, homozygotes show a severe reduction in the extent of kainate-induced lesions in the CA3 subfield of the hippocampus, with a reduced distribution of TUNEL-positive and GFAP-positive astroglial fibers relative to wild-type mice

• no differences in JNK activation is observed following exposure to ultraviolet radiation or treatment with the drug anisomycin

abnormal NMDA-mediated synaptic currents ( J:125318 )

• NMDA-mediated current amplitude is decreased relative to in wild-type mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:77616 )

N • contrary to expectations, homozygotes display normal islet morphology, normal expression of insulin and glucagon, as well as normal blood glucose levels and performance in glucose tolerance tests relative to wild-type mice

decreased susceptibility to neuronal excitotoxicity ( J:77616 )

• in vitro, mutant hippocampal neurons exhibit reduced stress-induced apoptosis following exposure to the excitotoxin kainate

• mutant neurons are also resistant to the apoptotic effects of anoxic stress induced by oxygen-glucose deprivation, as shown by reduced labeling in TUNEL assays and increased cell survival

• following exposure to kainite-induced excitotoxic stress, mutant hippocampal neurons display attenuated JNK activation despite a normal level of Jun protein expression

• in vivo, homozygotes show a severe reduction in the extent of kainate-induced lesions in the CA3 subfield of the hippocampus, with a reduced distribution of TUNEL-positive and GFAP-positive astroglial fibers relative to wild-type mice

• no differences in JNK activation is observed following exposure to ultraviolet radiation or treatment with the drug anisomycin

cellular

decreased susceptibility to neuronal excitotoxicity ( J:77616 )

• in vitro, mutant hippocampal neurons exhibit reduced stress-induced apoptosis following exposure to the excitotoxin kainate

• mutant neurons are also resistant to the apoptotic effects of anoxic stress induced by oxygen-glucose deprivation, as shown by reduced labeling in TUNEL assays and increased cell survival

• following exposure to kainite-induced excitotoxic stress, mutant hippocampal neurons display attenuated JNK activation despite a normal level of Jun protein expression

• in vivo, homozygotes show a severe reduction in the extent of kainate-induced lesions in the CA3 subfield of the hippocampus, with a reduced distribution of TUNEL-positive and GFAP-positive astroglial fibers relative to wild-type mice

• no differences in JNK activation is observed following exposure to ultraviolet radiation or treatment with the drug anisomycin

Genotype
MGI:4360031

cx2

• Allelic Composition: Mapk8ip1^tm1Rjd/Mapk8ip1^tm1Rjd; Mapk8ip2^tm1Rjd/Mapk8ip2^tm1Rjd
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ

mortality/aging

postnatal lethality, complete penetrance ( J:152617 )

• within 2 weeks of birth

growth/size/body

growth/size/body region phenotype ( J:152617 )

N • mice exhibit normal growth

decreased body size ( J:152617 )

• at P2 and P10

decreased body weight ( J:152617 )

• at P10

postnatal growth retardation ( J:152617 )

• severe

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:152617 )

N • despite abnormal beta cell morphology, mice exhibit normal blood insulin concentration

hypoglycemia ( J:152617 )

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:152617 )

• beta cells exhibit fewer exocytotic vesicles compared with wild-type cells

Genotype
MGI:3759994

cx3

• Allelic Composition: Mapk8ip1^tm1Rjd/Mapk8ip1^tm1Rjd; Mapk8ip2^tm1Rjd/Mapk8ip2^tm1Rjd
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6

nervous system

abnormal cerebellum morphology ( J:125318 )

• mice exhibit defects in the cerebellum

abnormal Purkinje cell morphology ( J:125318 )

• mice have defects in arborization of Purkinje cell

• however, cortical and hippocampal neurons are normal

abnormal NMDA-mediated synaptic currents ( J:125318 )

• treatment with NMDA fails to cause an increase in cytoplasmic calcium in neurons unlike in wild-type mice

• NMDA-mediated current amplitude is decreased relative to in wild-type mice

• desensitization of the NMDA-mediated current is reduced relative to in wild-type mice

• however, intracellular calcium homeostasis is normal

behavior/neurological

ataxia ( J:125318 )

• mice are severely ataxic