Phenotypes for Gpc3 MGI:3530365 MGI Mouse

postnatal lethality, complete penetrance ( J:73877 )

• by N8, all mutants die prior to weaning; all studies described are performed in mice obtained from backcrosses N7 to N9 with C57BL/6

postnatal lethality, incomplete penetrance ( J:73877 )

• 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

mandible hypoplasia ( J:73877 )

• 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

increased body weight ( J:73877 )

• hemizygous males exhibit a significant developmental overgrowth relative to wild-type mice

• at birth, hemizygotes are 30% heavier than wild-type

kidney cyst ( J:67732 , 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)

enlarged kidney ( J:73877 )

• at E13.5, mutant kidneys are significantly larger than wild-type kidneys

increased lung weight ( 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

homeostasis/metabolism phenotype ( J:73877 )

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

lung inflammation ( J:73877 )

• 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

rhinitis ( J:73877 )

• mutants from N2 to N4 that die before weaning exhibit rhinitis

increased susceptibility to bacterial infection ( J:73877 )

• mutants develop respiratory infections with a higher frequency than wild-type mice

kidney cyst ( J:67732 , 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)

enlarged kidney ( J:73877 )

• at E13.5, mutant kidneys are significantly larger than wild-type kidneys

abnormal kidney collecting duct morphology ( J:67732 )

• at E16.5, mutant cortical collecting duct (CCD) cells show a 3-fold increase in cell proliferation relative to wild-type CCD cells

abnormal kidney cortex morphology ( J:73877 )

• by E16.5, cortical tissue elements (glomeruli and tubules) are present but appear disorganized

abnormal kidney development ( J:73877 )

• 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

abnormal kidney medulla morphology ( J:67732 , 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)

abnormal kidney weight ( 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

abnormal ureteric bud morphology ( 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

abnormal branching involved in ureteric bud morphogenesis ( 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