PMID- 10319319
OWN - NLM
STAT- MEDLINE
DCOM- 19990708
LR  - 20111117
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 13
IP  - 5
DP  - 1999 May
TI  - Targeted disruption of the Insl3 gene causes bilateral cryptorchidism.
PG  - 681-91
AB  - The sexual dimorphic position of the gonads in mammals is dependent on
      differential development of two ligaments, the cranial suspensory ligament (CSL) 
      and the gubernaculum. During male embryogenesis, outgrowth of the gubernaculum
      and regression of the CSL result in transabdominal descent of the testes, whereas
      in the female, development of the CSL in conjunction with failure of the
      gubernaculum development holds the ovaries in a position lateral to the kidneys. 
      Several lines of evidence suggest that regression of the CSL and induction of
      gubernaculum development are mediated by testosterone and a yet unidentified
      testicular factor, respectively. The Insl3 gene (originally designated Ley I-L), 
      a member of the insulin-like superfamily, is specifically expressed in Leydig
      cells of the fetal and postnatal testis and in theca cells of the postnatal
      ovary. Here we show that male mice homozygous for a targeted deletion of the
      Insl3 locus exhibit bilateral cryptorchidism with free moving testes and genital 
      ducts. These malformations are due to failure of gubernaculum development during 
      embryogenesis. In double-mutant male mice for Insl3 and androgen receptor genes, 
      testes are positioned adjacent to the kidneys and steadied in the abdomen by the 
      CSL. These findings demonstrate, that the Insl3 induces gubernaculum development 
      in an androgen-independent way, while androgen-mediated regression of the CSL
      occurs independently from Insl3.
FAU - Zimmermann, S
AU  - Zimmermann S
AD  - Institut fur Humangenetik der Universitat Gottingen, Germany.
FAU - Steding, G
AU  - Steding G
FAU - Emmen, J M
AU  - Emmen JM
FAU - Brinkmann, A O
AU  - Brinkmann AO
FAU - Nayernia, K
AU  - Nayernia K
FAU - Holstein, A F
AU  - Holstein AF
FAU - Engel, W
AU  - Engel W
FAU - Adham, I M
AU  - Adham IM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Androgens)
RN  - 0 (Insulin)
RN  - 0 (Leydig insulin-like protein)
RN  - 0 (Proteins)
SB  - IM
MH  - Androgens/physiology
MH  - Animals
MH  - Cryptorchidism/*genetics
MH  - Female
MH  - Homozygote
MH  - Infertility, Male/genetics
MH  - Insulin
MH  - Ligaments/growth & development
MH  - Male
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Mutation
MH  - Proteins/*genetics
MH  - Sex Differentiation/genetics
MH  - Spermatogenesis/genetics
MH  - Testis/*abnormalities/growth & development/pathology
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - 10.1210/mend.13.5.0272 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1999 May;13(5):681-91. doi: 10.1210/mend.13.5.0272.