The present invention relates generally to novel molecules capable of,
inter alia, modulating apoptosis in mammalian cells and to genetic
sequences encoding same. More particularly, the present invention relates
to a novel member of the Bcl-2 family of proteins, referred to herein as
"Bmf", and to genetic sequences encoding same and to regulatory sequences
such as a promoter sequence directing expression of Bmf. Bmf comprises a
BH3 domain which facilitates interaction to pro-survival Bcl-2 family
members thereby triggering apoptosis. Bmf is regarded, therefore, as a
BH3-only molecule. The molecules of the present invention are useful, for
example, in therapy, diagnosis, antibody generation and as a screening
tool for therapeutic agents capable of modulating physiological cell
death or survival and/or modulating cell cycle entry. The present
invention further contemplates genetically modified animals in which one
or both alleles of Bmf are mutated or partially or wholly deleted alone
or in combination with a mutation in one or both alleles of another
Bcl-2-type molecule such as but not limited to Bim. The genetically
modified animals are useful inter alia in screening for agents which
ameliorate the symptoms of diseases caused by defects in apoptosis or
which specifically promote apoptosis of target cells.