TY - JOUR
T1 - Mouse Tdho abnormality results from double point mutations of the emopamil binding protein gene (Ebp)
AU - Seo, Kwang Won
AU - Kelley, Richard I.
AU - Okano, Shinya
AU - Watanabe, Tomomasa
PY - 2001
Y1 - 2001
N2 - 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-3β-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 responsine for Tdho as well as Td are quite similar to those of human X-linked chondrodysplasia punctata (CDPX2).
AB - 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-3β-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 responsine for Tdho as well as Td are quite similar to those of human X-linked chondrodysplasia punctata (CDPX2).
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U2 - 10.1007/s00335-001-3010-1
DO - 10.1007/s00335-001-3010-1
M3 - Article
C2 - 11471053
AN - SCOPUS:0034920669
SN - 0938-8990
VL - 12
SP - 602
EP - 605
JO - Mammalian Genome
JF - Mammalian Genome
IS - 8
ER -