Mouse Genome Informatics
hm1
    Gpc3tm1Fil/Gpc3tm1Fil
B6.Cg-Gpc3tm1Fil
Key:
phenotype observed in females
phenotype observed in males
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

craniofacial

digestive/alimentary system
• mutant females with an imperforate vagina display swelling of the perineum

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

immune system

renal/urinary system

respiratory system

skeleton

growth/size/body


Mouse Genome Informatics
ht2
    Gpc3tm1Fil/Gpc3+
B6.Cg-Gpc3tm1Fil
Key:
phenotype observed in females
phenotype observed in males
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)
• the degree of renal dysplasia varies from mouse to mouse
• from N4 on, some heterozygous females display cystic kidneys (also noted in a large proportion of mice from earlier backcrosses)

growth/size/body
• heterozygotes display an intermediate size between hemizygous mutant males and wild-type controls at all time points

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
phenotype observed in males
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
• Background Sensitivity: a proportion of mutants survive beyond the first day, esp. in earlier backcrosses (N2 to N4)
• after N4, only 10% of males that can be typed are hemizygous (many are cannibalized); only 2 out of 21 survive to weaning

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

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

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

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
• as early as P0, the lumens of airways contain an admixture of stranding mucus and sloughed epithelial cells
• by P5, the entire surface of the respiratory epithelium is covered with mucus
• mutants from N2 to N4 that die before weaning exhibit rhinitis
• mutants develop respiratory infections with a higher frequency than wild-type mice

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
• by E16.5, cortical tissue elements (glomeruli and tubules) are present but appear disorganized
• from N4 on, all mutants display dysplastic kidneys (also noted in a large proportion of mice from earlier backcrosses)
• the degree of renal dysplasia varies from mouse to mouse
• 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
• notably, no significant weight differences are noted in kidney at E16.5, E18.5, and P0
• at E13.5, mutant kidneys are significantly larger than wild-type kidneys
• 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
• this developmental anomaly of the ureteric bud/collecting system is due to increased proliferation of cells in this tissue element
• in contrast, no significant differences in mesenchymal cell proliferation are noted at E12.5, E13.5 or E16.5
• 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

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

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

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