Mouse Genome Informatics
ht1
    H19tm1Tilg/H19+
involves: 129S/SvEv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• placentas are 54% heavier at E18.5 than in wild-type when the mutated allele is inherited maternally

growth/size/body
• heterozygotes inheriting the mutant allele from the mother exhibit an increase in body mass (28% difference from wild-type) (J:25091)
• heavier than controls at E18.5 when the mutated allele is inherited maternally (J:75054)

cellular
• defects are seen in heterozygotes that receive the mutant allele from the mother while those that receive the mutant allele from the father are normal (J:25091)
• when maternally inherited, the maternal H19 gene is repressed and the normally imprinted Igf2 and Ins-2 genes are expressed (J:25091)


Mouse Genome Informatics
ht2
    H19tm1.1Sriv/H19tm1Tilg
involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• methylation is altered such that maternal Igf2 is aberrantly expressed


Mouse Genome Informatics
cx3
    H19tm1Tilg/H19+
Sdhdtm1Jpb/Sdhd+

involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
N
• no paragangliomas nor pheochromocytomas are detected in mice at up to 29 months of age in contrast to expectations from human disease data (J:155380)

nervous system
N
• no significant changes in carotid body or the adrenal medulla are seen (J:155380)


Mouse Genome Informatics
cx4
    H19tm1Tilg/H19+
Igf2tm1Rob/Igf2+

involves: 129S/SvEv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
N
• indistinguishable in size from wild-type in birth weights and postnatal growth rates (J:25091)


Mouse Genome Informatics
cx5
    Gpc3tm1Arge/Y
H19tm1Tilg/H19+

involves: 129S/SvEv * 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• about 70% of double mutant males that inherit the H19 allele maternally are stillborn (J:75054)
• some additional mutants (that inherit the H19 allele maternally) that survive the perinatal period die before weaning (J:75054)

embryogenesis
• placentas are 94% heavier at E18.5 than in wild-type in double mutants that inherit the H19 allele maternally (J:75054)

growth/size/body
• double mutants that inherit the H19 allele maternally are heavier than wildtype at E18.5, but similar in weight as either single mutant (J:75054)
• seen in 13 of 16 double mutants that inherit the H19 allele maternally (J:75054)

skeleton
• 3 of 6 double mutants that inherit the H19 allele maternally exhibit asymmetrical and staggered attachment of the ribs to the sternum (J:75054)
• ossification of the sternum throughout its length (J:75054)
• in 3 of 6 mutants double mutants that inherit the H19 allele maternally, the cartilage of the xiphisternum is bifurcated (J:75054)
• one severely affected double mutant with the fusion of the first two ribs also has an extra (14th) pair of rudimentary ribs associated with the first pair of lumbar vertebrae (J:75054)
• one severely affected double mutant shows unilateral fusion of the first two ribs in the middle portion (J:75054)

cellular
• defects are seen in double mutants that receive the H19 mutant allele from the mother (J:75054)

Mouse Models of Human Disease
OMIM IDRef(s)
Simpson-Golabi-Behmel Syndrome, Type 1; SGBS1 312870 J:75054


Mouse Genome Informatics
cx6
    Gpc3tm1Arge/Gpc3tm1Arge
H19tm1Tilg/H19+

involves: 129S/SvEv * 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• about 70% of double mutants that inherit the H19 allele maternally are stillborn (J:75054)
• some additional mutants (that inherit the H19 allele maternally) that survive the perinatal period die before weaning (J:75054)

cellular
• defects are seen in double mutants that receive the H19 mutant allele from the mother (J:75054)


Mouse Genome Informatics
cx7
    Dnmt1tm1Enl/Dnmt1tm1Enl
H19tm1Tilg/H19+

involves: 129S/SvEv * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• Ifg2 expression is normal indicating that imprinting is normal at this locus


Mouse Genome Informatics
cx8
    H19tm1Tilg/H19+
Tg(CRP-TAg)60-3Urt/0

involves: 129S/SvEv * BALB/c * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice with paternal inheritance of H19tm1Lda live longer than those expressing only Tg(CRP-TAg)60-3Urt (J:90036)

tumorigenesis
• by 6 months mice with paternal inheritance of H19tm1Lda develop liver tumors unlike in wild-type mice
• when H19tm1Lda is inherited paternally, mice display a more than 3 week delay in spontaneous tumorigenesis and subsequent mortality associated with Tg(CRP-TAg)60-3Urt expression