Compositions and methods for increasing animal size growth rate
The present invention relates to germ line and somatic cells comprising a mutant p27 kip1 protein lacking a Cdk2 phosphorylation site. Also provided are transgenic animals and methods of making such transgenic animals which have increased size and/or growth rate.
1. An isolated transgenic somatic or embryonic stem cell having a mutant p27 Kip1 gene lacking a Cdk2 phosphorylation site integrated at the endogenous p27 Kip1 gene such that there is a loss of endogenous wildtype p27 Kip1 activity, wherein the mutant p27 Kip1 gene encodes a mutant p27 Kip1 polypeptide having a longer half-life in S phase than wildtype p27 Kip1 polypeptide.
2. The transgenic cell of claim 1 , wherein the mutant p27 Kip1 polypeptide inhibits Cdk2 in vitro kinase activity.
3. The transgenic cell of claim 1 , wherein the mutant p27 Kip1 polypeptide is p27 T187A .
4. An isolated transgenic mouse cell having a mutant p27 Kip1 gene lacking a Cdk2 phosphorylation site integrated at the endogenous p27 Kip1 gene such that there is a loss of endogenous wildtype p27 Kip1 activity, wherein the mutant p27 Kip1 gene encodes a mutant p27Kip1polypeptide having a longer half-life in S phase than wild-type p27 Kip1 1 polypeptide.
5. The isolated transgenic mouse cell of claim 4 , wherein the cell is a somatic cell, a germ cell, a fertilized egg, or an embryonic stem cell.
6. The isolated transgenic mouse cell of claim 5 , wherein the germ cell is a an oocyte, primordial germ cell, sperm cell, or spermatocyte.