Home LiteratureArticle Details
PMID: 12370412 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 21 ·2002-10-15 ·Pages 13498-503

Yeh S, Tsai MY, Xu Q, Mu XM, Lardy H, Huang KE, Lin H, Yeh SD, Altuwaijri S, Zhou X, Xing L, Boyce BF, Hung MC, Zhang S, Gan L, Chang C, Hung MC

Abstract

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.

MeSH Terms
Adipose Tissue/abnormalities Androgens/physiology Animals Body Weight Bone and Bones/abnormalities Female Gene Targeting Genitalia, Male/abnormalities Heterozygote Homozygote Integrases/genetics Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Models, Biological Pregnancy Receptors, Androgen/deficiency,genetics,physiology Sex Characteristics Spermatogenesis/genetics,physiology Testis/abnormalities Testosterone/blood Viral Proteins/genetics
Chemicals
Androgens Receptors, Androgen Viral Proteins Testosterone Cre recombinase Integrases
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Yeh Shuyuan
Departments of Urology and Pathology, George H. Whipple Lab for Cancer Research, University of Rochester, Rochester, NY 14642, USA.
Tsai Meng-Yin
Xu Qingquan
Mu Xiao-Min
Lardy Henry
Huang Ko-En
Lin Hank
Yeh Shauh-Der
Altuwaijri Saleh
Zhou Xinchang
Xing Lianping
Boyce Brendan F
Hung Mien-Chie
Zhang Su
Gan Lin
Chang Chawnshang
Hung Min-Chi
References (44)
44 references, click to expand
  1. The expansion of the CAG repeat in exon 1 of the human androgen receptor gene is associated with uterine endometrial carcinoma.
    Mol Carcinog. 2000 Mar;27(3):237-44 PMID: 10708486
  2. Steroid-induced androgen receptor-oestradiol receptor beta-Src complex triggers prostate cancer cell proliferation.
    EMBO J. 2000 Oct 16;19(20):5406-17 PMID: 11032808
  3. Comparative effects of estrogens plus androgens and tibolone on bone, lipid pattern and sexuality in postmenopausal women.
    Maturitas. 2000 Feb 15;34(2):161-8 PMID: 10714911
  4. Interactions between androgen and estrogen receptors and the effects on their transactivational properties.
    Mol Cell Endocrinol. 2000 Sep 25;167(1-2):139-50 PMID: 11000528
  5. Requirement for math5 in the development of retinal ganglion cells.
    Genes Dev. 2001 Jan 1;15(1):24-9 PMID: 11156601
  6. Sex steroids and bone.
    Physiol Rev. 2001 Jan;81(1):419-447 PMID: 11152762
  7. Genetic evidence for a role for Src family kinases in TNF family receptor signaling and cell survival.
    Genes Dev. 2001 Jan 15;15(2):241-53 PMID: 11157779
  8. 17beta-estradiol stimulates expression of osteoprotegerin by a mouse stromal cell line, ST-2, via estrogen receptor-alpha.
    Endocrinology. 2001 Jun;142(6):2205-12 PMID: 11356664
  9. A single vector containing modified cre recombinase and LOX recombination sequences for inducible tissue-specific amplification of gene expression.
    Nucleic Acids Res. 2001 Jun 15;29(12):E56-6 PMID: 11410679
  10. Effects of androgens on T and B lymphocyte development.
    Immunol Res. 2001;23(2-3):281-8 PMID: 11444393
  11. Diagnosis and localization of testosterone-producing ovarian tumors: imaging or biochemical evaluation.
    Gynecol Oncol. 2001 Dec;83(3):596-8 PMID: 11733978
  12. Domain interactions between coregulator ARA(70) and the androgen receptor (AR).
    Mol Endocrinol. 2002 Feb;16(2):287-300 PMID: 11818501
  13. Roles of androgens in the development, growth, and carcinogenesis of the mammary gland.
    J Steroid Biochem Mol Biol. 2002 Feb;80(2):175-89 PMID: 11897502
  14. Androgen receptor (AR) coregulators: an overview.
    Endocr Rev. 2002 Apr;23(2):175-200 PMID: 11943742
  15. NF-kappaB p50 and p52 expression is not required for RANK-expressing osteoclast progenitor formation but is essential for RANK- and cytokine-mediated osteoclastogenesis.
    J Bone Miner Res. 2002 Jul;17(7):1200-10 PMID: 12096833
  16. Testosterone metabolism in human bone.
    Acta Endocrinol (Copenh). 1980 Oct;95(2):258-64 PMID: 7435119
  17. Molecular cloning of human and rat complementary DNA encoding androgen receptors.
    Science. 1988 Apr 15;240(4850):324-6 PMID: 3353726
  18. Cloning of human androgen receptor complementary DNA and localization to the X chromosome.
    Science. 1988 Apr 15;240(4850):327-30 PMID: 3353727
  19. Structural analysis of complementary DNA and amino acid sequences of human and rat androgen receptors.
    Proc Natl Acad Sci U S A. 1988 Oct;85(19):7211-5 PMID: 3174628
  20. High-affinity androgen binding and androgenic regulation of alpha 1(I)-procollagen and transforming growth factor-beta steady state messenger ribonucleic acid levels in human osteoblast-like osteosarcoma cells.
    Endocrinology. 1991 Jun;128(6):2723-30 PMID: 2036957
  21. A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse.
    Nucleic Acids Res. 1991 May 11;19(9):2373-8 PMID: 2041777
  22. Androgen regulation of spermatogenesis in the rat.
    Ann N Y Acad Sci. 1991;637:90-106 PMID: 1785793
  23. Sex-specific response of bone cells to gonadal steroids: modulation in perinatally androgenized females and in testicular feminized male rats.
    Steroids. 1993 Mar;58(3):126-33 PMID: 8475517
  24. A novel phage lambda replacement Cre-lox vector that has automatic subcloning capabilities.
    Gene. 1993 Oct 29;133(1):95-7 PMID: 8224901
  25. Androgen receptor distribution in rat testis: new implications for androgen regulation of spermatogenesis.
    Endocrinology. 1994 May;134(5):2307-16 PMID: 8156934
  26. Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation.
    Endocrinology. 1994 Aug;135(2):798-800 PMID: 8033830
  27. Immunocytochemical identification of androgen receptor in mouse osteoclast-like multinucleated cells.
    Calcif Tissue Int. 1994 Apr;54(4):325-6 PMID: 8062148
  28. Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality.
    Maturitas. 1995 Apr;21(3):227-36 PMID: 7616872
  29. Androgen receptor: an overview.
    Crit Rev Eukaryot Gene Expr. 1995;5(2):97-125 PMID: 8845584
  30. Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells.
    Proc Natl Acad Sci U S A. 1996 May 28;93(11):5517-21 PMID: 8643607
  31. Osteopenia as a feature of the androgen insensitivity syndrome.
    Clin Endocrinol (Oxf). 1995 Dec;43(6):671-5 PMID: 8736267
  32. Increased bone formation in osteocalcin-deficient mice.
    Nature. 1996 Aug 1;382(6590):448-52 PMID: 8684484
  33. Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-beta.
    Nat Med. 1996 Oct;2(10):1132-6 PMID: 8837613
  34. Adipocyte differentiation: a transcriptional regulatory cascade.
    Curr Opin Cell Biol. 1996 Dec;8(6):826-32 PMID: 8939673
  35. The antiovulatory effect of the antiprogestin onapristone could be related to down-regulation of intraovarian progesterone (receptors).
    J Steroid Biochem Mol Biol. 1997 May;62(1):107-18 PMID: 9366504
  36. From estrogen to androgen receptor: a new pathway for sex hormones in prostate.
    Proc Natl Acad Sci U S A. 1998 May 12;95(10):5527-32 PMID: 9576916
  37. Androgen receptors in human preadipocytes and adipocytes: regional specificities and regulation by sex steroids.
    Am J Physiol. 1998 Jun;274(6 Pt 1):C1645-52 PMID: 9611130
  38. Ovarian androgens protect against bone loss in rats made oestrogen deficient by treatment with ICI 182,780.
    J Endocrinol. 1999 Jan;160(1):111-7 PMID: 9858876
  39. Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma.
    J Biol Chem. 1999 Jun 4;274(23):16147-52 PMID: 10347167
  40. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families.
    Endocr Rev. 1999 Jun;20(3):345-57 PMID: 10368775
  41. Androgens promote oocyte insulin-like growth factor I expression and initiation of follicle development in the primate ovary.
    Biol Reprod. 1999 Aug;61(2):353-7 PMID: 10411511
  42. Androgen-activating enzymes in the central nervous system.
    J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):117-22 PMID: 10418985
  43. Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development.
    J Clin Endocrinol Metab. 1999 Aug;84(8):2951-6 PMID: 10443703
  44. Androgen receptor agonist activity of the synthetic progestin, medroxyprogesterone acetate, in human breast cancer cells.
    Mol Cell Endocrinol. 1999 Aug 20;154(1-2):11-20 PMID: 10509795
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.212474399
Published
2002-10-15
Epub
2002-00-07
Pages
13498-503
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC129702
Subset
IM
Grants
NIAMS NIH HHS · R01 AR043510 · United States
NIDDK NIH HHS · R01 DK060905 · United States
NIAMS NIH HHS · AR 43510 · United States
NIDDK NIH HHS · DK 60905 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1073/pnas.212474399 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2