Loss of the imprinted IGF2/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality.
Murine embryos that inherit a nonfunctional insulin-like growth factor-II/cation-independent mannose 6-phosphate receptor (Igf2r) gene from their fathers are viable and develop normally into adults. However, the majority of mice inheriting the same mutated allele from their mothers die around birth, as a consequence of major cardiac abnormalities. These mice do not express IGF2R in their tissues, are 25-30% larger than their normal siblings, have elevated levels of circulating IGF2 and IGF-binding proteins, and exhibit a slight kink in their tails. These results show that Igf2r is paternally imprinted and reveal that the receptor is crucial for regulating normal fetal growth, circulating levels of IGF2, and heart development.
Lau
M M
MM
Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.
Stewart
C E
CE
Liu
Z
Z
Bhatt
H
H
Rotwein
P
P
Stewart
C L
CL
D000483:Alleles; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003433:Crosses, Genetic; D005314:Embryonic and Fetal Development; D005091:Exons; D005260:Female; D005313:Fetal Death; D005333:Fetus / Q000378:metabolism; D018392:Genomic Imprinting; D015698:Genomic Library; D006330:Heart Defects, Congenital / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D011863:Radioimmunoassay; D017527:Receptor, IGF Type 2 / Q000096:biosynthesis / Q000235:genetics*; D013234:Stem Cells / Q000502:physiology
D001786:Blood Glucose; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II