Mouse Genome Informatics
hm1
    Gpc3tm1Fil/Gpc3tm1Fil
B6.Cg-Gpc3tm1Fil
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• phenotype is stated to be similar to that of Gpc3tm1Fil male hemizygotes; however, no data are presented in J:73877 (J:73877)

craniofacial

digestive/alimentary system
• mutant females with an imperforate vagina display swelling of the perineum (J:73877)

reproductive system
• mutant females with an imperforate vagina display swelling of the perineum (J:73877)
• mutant females with an imperforate vagina have a dilated, fluid-filled uterus (J:73877)
• mutant females exhibit an imperforate vagina at a higher frequency (30%) than wild-type females (4%) (J:73877)

immune system

renal/urinary system
(J:73877)

respiratory system

skeleton

growth/size


Mouse Genome Informatics
ht2
    Gpc3tm1Fil/Gpc3+
B6.Cg-Gpc3tm1Fil
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Cystic and dysplastic kidneys in Gpc3tm1Fil/Gpc3+ mice

renal/urinary system
• from N4 on, some heterozygous females display dysplastic kidneys (also noted in a large proportion of mice from earlier backcrosses) (J:73877)
• the degree of renal dysplasia varies from mouse to mouse (J:73877)
• from N4 on, some heterozygous females display cystic kidneys (also noted in a large proportion of mice from earlier backcrosses) (J:73877)

growth/size
• heterozygotes display an intermediate size between hemizygous mutant males and wild-type controls at all time points (J:73877)

Mouse Models of Human Disease
OMIM IDRef(s)
Simpson-Golabi-Behmel Syndrome, Type 1; SGBS1 312870 J:73877


Mouse Genome Informatics
ot3
    Gpc3tm1Fil/Y
B6.Cg-Gpc3tm1Fil
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Some Gpc3tm1Fil/Y embryos exhibit mandibular hypoplasia

mortality/aging
• by N8, all mutants die prior to weaning; all studies described are performed in mice obtained from backcrosses N7 to N9 with C57BL/6 (J:73877)
• Background Sensitivity: a proportion of mutants survive beyond the first day, esp. in earlier backcrosses (N2 to N4) (J:73877)
• after N4, only 10% of males that can be typed are hemizygous (many are cannibalized); only 2 out of 21 survive to weaning (J:73877)

craniofacial
• 10% of mutants from N7 and N8 exhibit complete lack of mandible, with only myxomatous stroma and overlying haired skin in place of the rami of the mandible (J:73877)

growth/size
• hemizygous males exhibit a significant developmental overgrowth relative to wild-type mice (J:73877)
• at birth, hemizygotes are 30% heavier than wild-type (J:73877)

homeostasis/metabolism
N
• mutants exhibit normal IGF-II levels in serum, whole embryo, lung, liver, and kidney at all at developmental stages tested (J:73877)

immune system
• mutants from N2 to N4 that die before weaning exhibit pneumonia, with accumulation of cellular debris and mucus in small and medium size bronchioles (J:73877)
• as early as P0, the lumens of airways contain an admixture of stranding mucus and sloughed epithelial cells (J:73877)
• by P5, the entire surface of the respiratory epithelium is covered with mucus (J:73877)
• mutants from N2 to N4 that die before weaning exhibit rhinitis (J:73877)
• mutants develop respiratory infections with a higher frequency than wild-type mice (J:73877)

renal/urinary system
• at E16.5, mutant cortical collecting duct (CCD) cells show a 3-fold increase in cell proliferation relative to wild-type CCD cells (J:67732)
• by E16.5, cortical tissue elements (glomeruli and tubules) are present but appear disorganized (J:73877)
• from N4 on, all mutants display dysplastic kidneys (also noted in a large proportion of mice from earlier backcrosses) (J:73877)
• the degree of renal dysplasia varies from mouse to mouse (J:73877)
• at E16.5, mutants show a significant increase in apoptosis in medullary collecting duct (MCD) cells (16-fold) and in cuboidal cystic cells (1.6-fold) (J:67732)
• notably, cell proliferation in medullary cysts - but not in MCD cells - is increased by 4.9-fold in cuboidal cell cysts and 3.2-fold in squamous cell cysts (J:67732)
• by E15.5, the medulla of mutant kidneys begins to degenerate resulting in reduced whole kidney mass (J:73877)
• by E16.5, the mutant medulla is relatively devoid of tubular structures; epithelial cysts are found in an irregular pattern (J:73877)
• by E18.5, the medulla appears fully dysplastic: medullary tubules are reduced in number, disorganized, and often cystic (J:73877)
• at E13.5, mutant kidneys are disproportionally larger than wild-type kidneys (J:73877)
• notably, no significant weight differences are noted in kidney at E16.5, E18.5, and P0 (J:73877)
• at E13.5, mutant kidneys are significantly larger than wild-type kidneys (J:73877)
• at E16.5, two classes of epithelial cysts are identified in the medulla: cuboidal cell cysts and squamous cell cysts (J:67732)
• from N4 on, all mutants display cystic kidneys (also noted in a large proportion of mice from earlier backcrosses) (J:73877)
• mutants display overgrowth of the ureteric bud, but not the blastema-derived tissue elements, as early as day 1 after blastema induction (J:73877)
• this developmental anomaly of the ureteric bud/collecting system is due to increased proliferation of cells in this tissue element (J:73877)
• in contrast, no significant differences in mesenchymal cell proliferation are noted at E12.5, E13.5 or E16.5 (J:73877)
• starting at E12 and persisting through E16.5, mutant kidneys show enhanced branching of the ureteric bud, with a 3-fold increase of ureteric bud surface area in hemizygous kidneys (J:73877)

respiratory system
• mutants from N2 to N4 that die before weaning exhibit pneumonia, with accumulation of cellular debris and mucus in small and medium size bronchioles (J:73877)
• as early as P0, the lumens of airways contain an admixture of stranding mucus and sloughed epithelial cells (J:73877)
• by P5, the entire surface of the respiratory epithelium is covered with mucus (J:73877)
• mutants from N2 to N4 that die before weaning exhibit rhinitis (J:73877)
• at birth, mutant lungs weigh 28% more than wild-type lungs probably due to debris accumulation, as no disproportionate overgrowth is observed thereafter (J:73877)

skeleton
• 10% of mutants from N7 and N8 exhibit complete lack of mandible, with only myxomatous stroma and overlying haired skin in place of the rami of the mandible (J:73877)

Mouse Models of Human Disease
OMIM IDRef(s)
Simpson-Golabi-Behmel Syndrome, Type 1; SGBS1 312870 J:73877