title: Mouse Tdho abnormality results from double point mutations of the emopamil binding protein gene (Ebp).
abstract: Mouse Tdho (Tattered-Hokkaido) was described as being allelic with Td in our previous study. Both allelic genes, which are located at the same position on the centromere of the X Chromosome (Chr), generate similar phenotypes such as male embryonic lethality, and in heterozygous females, hyperkeratotic skin, skeletal abnormalities, and growth retardation. The emopamil binding protein gene (Ebp) emerged as a candidate for mouse Tdho mutation, since the Td gene was recently determined to result from a point mutation of Ebp. In this study, Ebp cDNA of Tdho was demonstrated to possess double point mutations that cause two amino acid changes from Leu to Pro at position 132 and from Ser to Cys at 133 in EBP protein. EBP participates in cholesterol biosynthesis, and cholest-8(9)-en-3beta-ol was found to be increased in the plasma of Tdho adult females but not in that of normal mice. From these results, a loss of function was expected for the EBP protein encoded by Tdho. Both the phenotypes and genes responsible for Tdho as well as Td are quite similar to those of human X-linked chondrodysplasia punctata (CDPX2).
authors.affiliation: Department of Experimental Animal Science, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: K W
authors.initials: KW
authors.lastname: Seo
authors.forename: R I
authors.initials: RI
authors.lastname: Kelley
authors.forename: S
authors.initials: S
authors.lastname: Okano
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D002806:Chondrodysplasia Punctata / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013251:Steroid Isomerases; D013261:Sterols / Q000096:biosynthesis / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; D013261:Sterols; C490380:Ebp protein, mouse; D013251:Steroid Isomerases