Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues.
By using a cre-lox conditional knockout strategy, we report here the generation of androgen receptor knockout (ARKO) mice. Phenotype analysis shows that ARKO male mice have a female-like appearance and body weight. Their testes are 80% smaller and serum testosterone concentrations are lower than in wild-type (wt) mice. Spermatogenesis is arrested at pachytene spermatocytes. The number and size of adipocytes are also different between the wt and ARKO mice. Cancellous bone volumes of ARKO male mice are reduced compared with wt littermates. In addition, we found the average number of pups per litter in homologous and heterozygous ARKO female mice is lower than in wt female mice, suggesting potential defects in female fertility and/or ovulation. The cre-lox ARKO mouse provides a much-needed in vivo animal model to study androgen functions in the selective androgen target tissues in female or male mice.
Yeh
Shuyuan
S
Departments of Urology and Pathology, George H. Whipple Lab for Cancer Research, University of Rochester, Rochester, NY 14642, USA.
Tsai
Meng-Yin
MY
Xu
Qingquan
Q
Mu
Xiao-Min
XM
Lardy
Henry
H
Huang
Ko-En
KE
Lin
Hank
H
Yeh
Shauh-Der
SD
Altuwaijri
Saleh
S
Zhou
Xinchang
X
Xing
Lianping
L
Boyce
Brendan F
BF
Hung
Mien-Chie
MC
Zhang
Su
S
Gan
Lin
L
Chang
Chawnshang
C
Hung
Min-Chi
MC
D000273:Adipose Tissue / Q000002:abnormalities; D000728:Androgens / Q000502:physiology; D000818:Animals; D001835:Body Weight; D001842:Bone and Bones / Q000002:abnormalities; D005260:Female; D018390:Gene Targeting; D005837:Genitalia, Male / Q000002:abnormalities; D006579:Heterozygote; D006720:Homozygote; D019426:Integrases / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D011247:Pregnancy; D011944:Receptors, Androgen / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012727:Sex Characteristics; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013737:Testis / Q000002:abnormalities; D013739:Testosterone / Q000097:blood; D014764:Viral Proteins / Q000235:genetics
D000728:Androgens; D011944:Receptors, Androgen; D014764:Viral Proteins; D013739:Testosterone; C045073:Cre recombinase; D019426:Integrases