Mice homozygous for the forebrain overgrowth recessive spontaneous mutation (fog) display forebrain, lumbo-sacral, and facial defects most likely due to excessive growth or cellular proliferation ultimately causing abnormalities in neural tube closure. The phenotypes manifest as head bumps and sacral spina bifida and individual mice can have either or both. Three unique features of the mutant are (1) the growth of telencephalon cells into the surrounding mesenchyme, (2) presence of an encephalocele through the midline cleft in some mutants, and (3) dissociation of the tail defect from the caudal neural tube defect. The fog mutation maps to mouse Chromosome 10 near D10Mit262 and D10Mit230.
|Allele Name||forebrain overgrowth|
|Allele Type||Spontaneous (Hypomorph)|
|Allele Synonym(s)||Apaf-1fog; fog|
|Gene Symbol and Name||Apaf1, apoptotic peptidase activating factor 1|
|Strain of Origin||STOCK Ggt1dwg/J|
|General Note||Mutant mice are characterized by forebrain overgrowth and excessive cellular proliferation in the midline cleft. Human APAF1 is a candidate gene for Noonan Syndrome (OMIM 163950), a complex disease with some patients showing facial, cardiac, retinal, and limb abnormalities reminiscent of defective apoptosis (J:49840).|
|Molecular Note||Defective mRNA processing appears to be the cause of the markedly reduced normal mRNA levels, protein levels, and activity in fog mutant mice. Complementation testing confirmed that the fog mutant mouse is an allele of Apaf1.|
When maintaining a live colony, heterozygous mice may be bred together or to wildtype mice from the colony. Heterozygous mice breed fine, but breeding heterozygous x heterozygous produces less than the expected 25% homozygotes in the offspring. In 1999, the donating investigator's lab reported that the few homozygotes which survive to adulthood are usually poor breeders - even though male meiosis appears normal at the light microscope level.
When using the forebrain overgrowth mouse strain in a publication, please cite the originating article(s) and include JAX stock #002979 in your Materials and Methods section.
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