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Phenotypes Associated with This Genotype
Genotype
MGI:3715267
Allelic
Composition
Gfra1tm1Jmi/Gfra1tm2Jmi
Tg(CAG-cre/Esr1*)5Amc/0
Genetic
Background
involves: 129/Sv * C57BL/6 * CBA * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gfra1tm1Jmi mutation (0 available); any Gfra1 mutation (5 available)
Gfra1tm2Jmi mutation (0 available); any Gfra1 mutation (5 available)
Tg(CAG-cre/Esr1*)5Amc mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• with 4-OHT treatment on E13.5 rather than E15.5, complete loss of enteric neurons in colon is still observed at E18.5, but no abnormalities in enteric ganglia of small intestine is seen
• fewer ENS progenitors are proliferating in the midgut at E13.5 in embryos treated with 4-OHT at E11.5 (12.2% vs 24% in controls)
• at E18.5, ganglion structure and innervation in the colon is completely disrupted relative to control mice with 4-OHT treatement at E15.5
• enteric ganglion cells die within 36 hours after 4-OHT treatment
• with 4-OHT treatment on E15.5, enteric ganglia and neurons are lost in the colon by birth
• abnormal thick nerve bundles are observed in the colons of E18.5 embryos after 4-hydroxytamoxifen, 4-OHT treatment on E15.5; this are likely un-defasciculated extrinsic nerve fibers

cellular
• nuclei of dying ganglion cells in mutants display numerous indentations in nuclear membrane, some with abnormal constriction of the nuclear membrane resulting in multilobation of the nuclei
• cells are shrunken with condensation of marginal heterochromatin and chromatin masses dispersed in the karyoplasms; diminuition of the cytoplasm and heterochromatin condensation in the nuclei are enhanced in ganglion cells in the myenteric layer
• enteric ganglion cells die within 36 hours of Gfra1 inactivation induced by 4-OHT treatment of pregnant females, but cell death is by mechanism other than apoptosis; enteric neuron death is not dependent on caspases or Bax
• some cells contain autolysosomes; almost no autophagosomes are detected in mutants at any stage of cell death
• fewer ENS progenitors are proliferating in the midgut at E13.5 in embryos treated with 4-OHT at E11.5 (12.2% vs 24% in controls)


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
03/13/2019
MGI 6.13
The Jackson Laboratory