PMID- 10402475
OWN - NLM
STAT- MEDLINE
DCOM- 19990809
LR  - 20220410
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 146
IP  - 1
DP  - 1999 Jul 12
TI  - Glypican-3-deficient mice exhibit developmental overgrowth and some of the
      abnormalities typical of Simpson-Golabi-Behmel syndrome.
PG  - 255-64
AB  - Glypicans are a family of heparan sulfate proteoglycans that are linked to the
      cell surface through a glycosyl-phosphatidylinositol anchor. One member of this
      family, glypican-3 (Gpc3), is mutated in patients with the Simpson-Golabi-Behmel 
      syndrome (SGBS). These patients display pre- and postnatal overgrowth, and a
      varying range of dysmorphisms. The clinical features of SGBS are very similar to 
      the more extensively studied Beckwith-Wiedemann syndrome (BWS). Since BWS has
      been associated with biallelic expression of insulin-like growth factor II
      (IGF-II), it has been proposed that GPC3 is a negative regulator of IGF-II.
      However, there is still no biochemical evidence indicating that GPC3 plays such a
      role.Here, we report that GPC3-deficient mice exhibit several of the clinical
      features observed in SGBS patients, including developmental overgrowth, perinatal
      death, cystic and dyplastic kidneys, and abnormal lung development. A proportion 
      of the mutant mice also display mandibular hypoplasia and an imperforate vagina. 
      In the particular case of the kidney, we demonstrate that there is an early and
      persistent developmental abnormality of the ureteric bud/collecting system due to
      increased proliferation of cells in this tissue element. The degree of
      developmental overgrowth of the GPC3-deficient mice is similar to that of mice
      deficient in IGF receptor type 2 (IGF2R), a well characterized negative regulator
      of IGF-II. Unlike the IGF2R-deficient mice, however, the levels of IGF-II in GPC3
      knockouts are similar to those of the normal littermates.
FAU - Cano-Gauci, D F
AU  - Cano-Gauci DF
AD  - The Ontario Cancer Institute, Toronto, Ontario, M5G 2M9 Canada.
FAU - Song, H H
AU  - Song HH
FAU - Yang, H
AU  - Yang H
FAU - McKerlie, C
AU  - McKerlie C
FAU - Choo, B
AU  - Choo B
FAU - Shi, W
AU  - Shi W
FAU - Pullano, R
AU  - Pullano R
FAU - Piscione, T D
AU  - Piscione TD
FAU - Grisaru, S
AU  - Grisaru S
FAU - Soon, S
AU  - Soon S
FAU - Sedlackova, L
AU  - Sedlackova L
FAU - Tanswell, A K
AU  - Tanswell AK
FAU - Mak, T W
AU  - Mak TW
FAU - Yeger, H
AU  - Yeger H
FAU - Lockwood, G A
AU  - Lockwood GA
FAU - Rosenblum, N D
AU  - Rosenblum ND
FAU - Filmus, J
AU  - Filmus J
LA  - eng
GR  - 37981/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Glypicans)
RN  - 0 (Heparan Sulfate Proteoglycans)
RN  - 0 (Proteoglycans)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
RN  - 9050-30-0 (Heparitin Sulfate)
SB  - IM
MH  - Abnormalities, Multiple/*genetics/physiopathology
MH  - Animals
MH  - Beckwith-Wiedemann Syndrome/genetics/physiopathology
MH  - Body Weight
MH  - Cell Division
MH  - Female
MH  - Genotype
MH  - Glypicans
MH  - Growth Disorders/*genetics/physiopathology
MH  - *Heparan Sulfate Proteoglycans
MH  - Heparitin Sulfate/*deficiency/genetics/physiology
MH  - Humans
MH  - Insulin-Like Growth Factor II/*analysis/genetics
MH  - Kidney Tubules, Collecting/abnormalities/embryology/pathology
MH  - Male
MH  - Mandible/abnormalities/embryology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Organ Size
MH  - Phenotype
MH  - Proteoglycans/*deficiency/genetics/physiology
MH  - Syndrome
PMC - PMC2199732
EDAT- 1999/07/14 00:00
MHDA- 1999/07/14 00:01
CRDT- 1999/07/14 00:00
PHST- 1999/07/14 00:00 [pubmed]
PHST- 1999/07/14 00:01 [medline]
PHST- 1999/07/14 00:00 [entrez]
AID - 10.1083/jcb.146.1.255 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Jul 12;146(1):255-64. doi: 10.1083/jcb.146.1.255.