• interestingly, adult homozygotes are viable and display no discernible defects

• no abnormalities in somite segmentation or cardiac looping are observed at E8.5

• by 10 months of age mutants have impaired performance in a novel object recognition test

• by 10 months of age some mutants show increased activity in an open field test

• a dramatic increase in apoptosis is seen in the degenerating forebrain

• by 10 months of age mutant mice start to show reduced body weights compared to wild-type

• the lateral ventricles are immensely enlarged compared to wild-type or single knockout mice

• the third ventricle is immensely enlarged compared to wild-type or single knockout mice

• the thickness of the corpus callosum is about a third that of controls

• the thickness of the molecular layers between the CA1 pyramidal cells and dentate gyrus is significantly reduced

• the cortex is about half the normal thickness and the 6 layers can no longer be distinguished

• increased Gfap expression indicates that reactive astrogliosis occurs along with forebrain degeneration

• changes in the expression of several markers indicate that neuronal atrophy occurs along with forebrain degeneration

• degeneration is seen in the forebrain

• double heterozygotes are viable and phenotypically normal

• mutant mice are viable and phenotypically normal

• double homozygotes die at E9-E9.5 probably due to cardiovascular failure

• at E8.5, double homozygotes display underdeveloped second branchial arches

• at E8.5, double homozygotes exhibit disorganization of the trunk paraxial mesoderm

• at E8.5, double homozygotes show a severe disorganization of the trunk ventral neural tube

• in some cases, the notochord is completely surrounded by disordered ventral neural tube cells

• at E8.5 and E9, double homozygotes display a delay in the closure of the anterior neuropore

• at E8.5-E9, double homozygotes exhibit a kinked neural tube

• at E8.5-E9, double homozygotes display abnormal somite segmentation

• at E9-E9.5, double homozygotes exhibit chorioallantoic fusion defects

• at E8.5, double homozygotes show a severe disorganization of the trunk ventral neural tube

• in some cases, the notochord is completely surrounded by disordered ventral neural tube cells

• at E8.5 and E9, double homozygotes display a delay in the closure of the anterior neuropore

• at E8.5-E9, double homozygotes exhibit a kinked neural tube

• at E8.5 and E9, double homozygotes display loss of mesenchyme cells in the presumptive midbrain

• at E8.5, double homozygotes show an apparent expanded forebrain

• at E8.5 and E9, double homozygotes exhibit unlooped hearts

• at E8.5, double homozygotes display underdeveloped second branchial arches

• mutant embryos die between E9.5 and E13.5

• at E9, mutant embryos display underdeveloped second branchial arches

• at E8.5, mutant embryos show a severe disorganization of the trunk ventral neural tube

• at E9, mutant embryos display a delay in the closure of the anterior neuropore

• at E8.5-E9, mutant embryos display a variable phenotype, ranging from no somite segmentation to the formation of highly disorganized somites

• at E8.5, mutant embryos show a severe disorganization of the trunk ventral neural tube

• at E9, mutant embryos display a delay in the closure of the anterior neuropore

• some mutant embryos exhibit heart looping delays at E8.5 and E9, whereas others show partial heart looping at E9

• at E9, mutant embryos display underdeveloped second branchial arches