Phenotypes Associated with This Genotype

Genotype
MGI:3715267

• Allelic Composition: Gfra1^tm1Jmi/Gfra1^tm2Jmi; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA * SJL

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

nervous system

nervous system phenotype ( J:122607 )

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

abnormal neuronal precursor proliferation ( J:122607 )

• 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)

abnormal enteric nervous system morphology ( J:122607 )

abnormal enteric ganglia morphology ( J:122607 )

• 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

absent enteric neurons ( J:122607 )

• with 4-OHT treatment on E15.5, enteric ganglia and neurons are lost in the colon by birth

abnormal nervous system development ( J:122607 )

• 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

abnormal cell nucleus morphology ( J:122607 )

• 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

abnormal cell death ( J:122607 )

• 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

abnormal neuronal precursor proliferation ( J:122607 )

• 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)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Hirschsprung's disease		DOID:10487	OMIM:600156 OMIM:606874 OMIM:606875 OMIM:608462 OMIM:611644	J:122607