Hutchinson-Gilford progeria syndrome (HGPS) is caused by the production of a 
truncated prelamin A, called progerin, which is farnesylated at its carboxyl 
terminus. Progerin is targeted to the nuclear envelope and causes misshapen 
nuclei. Protein farnesyltransferase inhibitors (FTI) mislocalize progerin away 
from the nuclear envelope and reduce the frequency of misshapen nuclei. To 
determine whether an FTI would ameliorate disease phenotypes in vivo, we created 
gene-targeted mice with an HGPS mutation (LmnaHG/+) and then examined the effect 
of an FTI on disease phenotypes. LmnaHG/+ mice exhibited phenotypes similar to 
those in human HGPS patients, including retarded growth, reduced amounts of 
adipose tissue, micrognathia, osteoporosis, and osteolytic lesions in bone. 
Osteolytic lesions in the ribs led to spontaneous bone fractures. Treatment with 
an FTI increased adipose tissue mass, improved body weight curves, reduced the 
number of rib fractures, and improved bone mineralization and bone cortical 
thickness. These studies suggest that FTIs could be useful for treating humans 
with HGPS.