Mutation of macrophage colony stimulating factor (Csf1) causes osteopetrosis in the tl rat.
Osteopetrosis results from a heterogeneous group of congenital bone diseases that display inadequate osteoclastic bone resorption. We recently mapped tl (toothless), a mutation that causes osteopetrosis in rats, to a genetic region predicted to include the rat Csf1 gene. In this study, we sequenced the coding sequence of the rat Csf1 gene to determine if a mutation in Csf1 could be responsible for the tl phenotype. Sequencing revealed a 10-base insertion in the coding sequence of mutant animals that produces a frameshift and generates a stop codon early in the mutant Csf1 coding sequence. The 41 amino acid polypeptide predicted to be produced from the Csf1 promoter would have only the first nine amino acids of the wild-type rat protein. These data suggest that osteopetrosis develops in tl/tl rats because they cannot produce functional mCsf, a growth factor required for osteoclast differentiation and activation.
Dobbins
David E
DE
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA. ddobbins@usuhs.mil
Sood
Raman
R
Hashiramoto
Akira
A
Hansen
Carl T
CT
Wilder
Ronald L
RL
Remmers
Elaine F
EF
D000595:Amino Acid Sequence; D000818:Animals; D020296:Animals, Congenic; D001483:Base Sequence; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010022:Osteopetrosis / Q000235:genetics*; D021101:Radiation Hybrid Mapping; D051381:Rats; D011917:Rats, Inbred Lew; D011922:Rats, Mutant Strains; D016415:Sequence Alignment
D016173:Macrophage Colony-Stimulating Factor