Phenotypes associated with this allele

• Allele Symbol: Gpt2^{tm1a(KOMP)Wtsi}
• Allele Name: targeted mutation 1a, Wellcome Trust Sanger Institute
• Allele ID: MGI:4363039
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gpt2^tm1a(KOMP)Wtsi/Gpt2^tm1a(KOMP)Wtsi	involves: C57BL/6J * C57BL/6N	MGI:5822779

Genotype
MGI:5822779

hm1

• Allelic Composition: Gpt2^{tm1a(KOMP)Wtsi}/Gpt2^{tm1a(KOMP)Wtsi}
• Genetic Background: involves: C57BL/6J * C57BL/6N
• Cell Lines: EPD0041_2_C04

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

Reduction in brain size in Gpt2^{tm1a(KOMP)Wtsi}/Gpt2^{tm1a(KOMP)Wtsi} mice

mortality/aging

premature death ( J:238353 )

• although born in the expected Mendelian ratio, mice grow sickly and die between P18 and P26

behavior/neurological

decreased locomotor activity ( J:238353 )

• at ~P18, mice begin to exhibit reduced motor activity

nervous system

abnormal brain development ( J:238353 )

• mice exhibit reduced postnatal brain growth

decreased brain size ( J:238353 )

• at P18-P22, combined areas of cortex, midbrain and cerebellum show a 13% decrease in area relative to wild-type controls

• however, brain size is grossly normal at birth

abnormal cerebral hemisphere morphology ( J:238353 )

• at P18-P22, brains show a significant reduction in the width across the two hemispheres, in the midline anterior-posterior distance, and in the diagonal length of both the left and right hemisphere

abnormal hippocampus neuron morphology ( J:238353 )

• at 10-14 days in vitro (DIV), hippocampal neurons show a 30% reduction in the number of synapses, as visualized by SV2-positive puncta

abnormal cerebral cortex morphology ( J:238353 )

• at P18-P22, brains show a small but significant reduction in cortical area (expressed as a percentage of total brain area) relative to wild-type controls

abnormal synapse morphology ( J:238353 )

• at 10-14 days in vitro (DIV), hippocampal neurons show a 30% reduction in the number of synapses, as visualized by SV2-positive puncta, suggesting defects in synapse formation

homeostasis/metabolism

abnormal amino acid level ( J:238353 )

• cultured mouse embryonic fibroblasts (MEFs) show near-complete loss of alanine secretion into the media and markedly reduced transfer of 15N from [alpha-15N]glutamine to alanine

• following culture with [U-13C]glucose, MEFs show reduced 13C labeling in alanine

abnormal metabolism ( J:238353 )

• at P18, brains show abnormal metabolomics signatures involving neuroprotective mechanisms; glutathione, folate and cysteine levels are decreased, whereas cystathionine levels are markedly increased

• increased cystathionine levels are also found in newborn P0 brains

abnormal amino acid metabolism ( J:238353 )

• at P18, brains show defects in amino acid metabolism such as low alanine levels and increased levels of several essential amino acids, including phenylalanine

• urea is markedly decreased at P18, suggesting a decrease in production of amine groups

• interestingly, alanine (a primary metabolite in the Gpt2 reaction) is upregulated in brain at P0 but downregulated at P18

abnormal enzyme/coenzyme activity ( J:238353 )

• at P18, brain lysates show significantly reduced total brain glutamic pyruvic transaminase (GPT) enzyme activity

cellular

abnormal tricarboxylic acid cycle ( J:238353 )

• at P18, brains show abnormal metabolomics signatures in glutamine-dependent anaplerotic processes involved in TCA cycle intermediates; 5 of 8 TCA cycle intermediates are markedly decreased, including citrate, isocitrate, succinate, fumarate, and malate

• unexpectedly, acetyl-CoA as well as ATP and GTP levels are elevated