Skewed X-inactivation in cloned mice.
In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P<0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders.
Senda
Sho
S
Laboratory of Cellular Biochemistry, Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Wakayama
Teruhiko
T
Yamazaki
Yukiko
Y
Ohgane
Jun
J
Hattori
Naka
N
Tanaka
Satoshi
S
Yanagimachi
Ryuzo
R
Shiota
Kunio
K
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D001921:Brain / Q000502:physiology; D003001:Cloning, Molecular; D019976:Cloning, Organism / Q000379:methods*; D004247:DNA / Q000235:genetics*; D030561:Databases, Nucleic Acid; D005260:Female; D007422:Intestines / Q000502:physiology; D007668:Kidney / Q000502:physiology; D008168:Lung / Q000502:physiology; D051379:Mice; D008957:Models, Genetic; D012016:Reference Values; D015183:Restriction Mapping; D012729:Sex Chromosome Aberrations; D014960:X Chromosome / Q000235:genetics
D004247:DNA