title: Mutation of macrophage colony stimulating factor (Csf1) causes osteopetrosis in the tl rat.
abstract: 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.
authors.affiliation: 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
authors.forename: David E
authors.initials: DE
authors.lastname: Dobbins
authors.forename: Raman
authors.initials: R
authors.lastname: Sood
authors.forename: Akira
authors.initials: A
authors.lastname: Hashiramoto
authors.forename: Carl T
authors.initials: CT
authors.lastname: Hansen
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Wilder
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Remmers
mesh_terms: 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
chemical_list: D016173:Macrophage Colony-Stimulating Factor