Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-8-25
pubmed:abstractText
WNT/CTNNB1 signaling is involved in the regulation of multiple embryonic developmental processes, adult tissue homeostasis, abd cell fate determination and differentiation. Many WNTs and components of the WNT/CTNNB1 signaling pathway are expressed in the testis, but their physiological roles in this organ are largely unknown. To elucidate the role(s) of WNT/CTNNB1 signaling in the testis, transgenic Ctnnb1 tm1Mmt/+;Amhr2 tm3(cre)Bhr/+ mice were generated to obtain sustained activation of the WNT/CTNNB1 pathway in both Leydig and Sertoli cells. Male Ctnnb1 tm1Mmt/+;Amhr2 tm3(cre)Bhr/+ mice were sterile because of testicular atrophy starting at 5 wk of age, associated with degeneration of seminiferous tubules and the progressive loss of germ cells. Although Cre activity was expected in Ctnnb1 tm1Mmt/+;Amhr2 tm3(cre)Bhr/+ Leydig cells, no evidence of Cre-mediated recombination of the floxed allele or of WNT/CTNNB1 pathway activation could be obtained, and testosterone levels were comparable to age-matched controls, suggesting that genetic recombination was inefficient in Leydig cells. Conversely, sustained WNT/CTNNB1 pathway activation was obtained in Ctnnb1 tm1Mmt/+;Amhr2 tm3(cre)Bhr/+ Sertoli cells. The latter often exhibited morphological characteristics suggestive of incomplete differentiation that appeared in a manner coincident with germ cell loss, and this was accompanied by an increase in the expression of the immature Sertoli cell marker AMH. In addition, a poorly differentiated, WT1-positive somatic cell population accumulated in multilayered foci near the basement membrane of many seminiferous tubules. Together, these data suggest that the WNT/CTNNB1 pathway regulates Sertoli cell functions critical to their capacity to support spermatogenesis in the postnatal testis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-3363
pubmed:author
pubmed:issnType
Print
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
475-85
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Seminiferous tubule degeneration and infertility in mice with sustained activation of WNT/CTNNB1 signaling in sertoli cells.
pubmed:affiliation
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural