C3.B6-Phactr4^humdy/J

Stock number: 016975
Research areas: Developmental Biology Research, Sensorineural Research

Description

Humpty dumpty (hmdy) is an ENU-generated point mutation of the Phactr4 (phosphatase and actin regulator 4)gene. Phenotypic traits include a failure of the neural tube and optic fissure to close in homozygous embryos causing exencephaly and retinal coloboma.

Detailed description

Humpty dumpty (hmdy) is an ENU-generated point mutation of the Phactr4 (phosphatase and actin regulator 4) gene that does not affect expression. The neural tube and optic fissure of homozygous embryos fail to close, causing exencephaly and retinal coloboma. Cranial neurulation and eye defects are extensive due to misregulation of cell proliferation and differentiation. Overgrowth of brain tissue, neural retina, and retinal pigment epithelium have been attributed to decreased cell-cycle length and disrupted cell-cycle exit. Mutant mice show green gut with aganglionosis by embryonic day 18 (E18). Most homozygous embryos die by embryonic day 14.5 (E14.5), but a few survive to birth and die shortly thereafter.

Development

A conserved C terminal R650P (arginine to proline) recessive missense mutation incorporating a G to C base pair change was created by ENU mutagenesis of C57BL/6J mice. It was identified in a screen for morphological abnormalities at embryonic day 12.5 (E12.5). This strain was backcrossed to C3H/HeNCrl for more than 10 generations by the donating laboratory.

Allele

Symbol: Phactr4^humdy
Name: humpty dumpty
MGI accession ID: MGI:3720740
Generation method: Chemically induced (ENU)
Marker symbol: Phactr4
Marker name: phosphatase and actin regulator 4
Marker synonyms: 3110001B12Rik; C330013F19Rik; PPP1R124
Chromosome: 4
Strain of origin: C57BL/6J
Molecular note: A missense mutation changed arginine at amino acid position 650 to proline in the conserved C-terminal region.