Page "Apoptosis" Paragraph 33

The caspase proteins are integral parts of the apoptosis pathway, so it follows that knock-outs made have varying damaging results.

A caspase 9 knock-out leads to a severe brain malformation.

A caspase 8 knock-out leads to cardiac failure and thus embryonic lethality.

However, with the use of cre-lox technology, a caspase 8 knock-out has been created that exhibits an increase in peripheral T cells, an impaired T cell response, and a defect in neural tube closure.

Interestingly, these mice were found to be resistant to apoptosis mediated by CD95, TNFR, etc.

but not resistant to apoptosis caused by UV irradiation, chemotherapeutic drugs, and other stimuli.

Finally, a caspase 3 knock-out was characterized by ectopic cell masses in the brain and abnormal apoptotic features such as membrane blebbing or nuclear fragmentation.

A remarkable feature of these KO mice is that they have a very restricted phenotype: Casp3, 9, APAF-1 KO mice have deformations of neural tissue and FADD and Casp 8 KO showed defective heart development, however in both types of KO other organs developed normally and some cell types were still sensitive to apoptotic stimuli suggesting that unknown proapoptotic pathways exist.