Caudal dysgenesis in Islet-1 transgenic mice.
Maternal diabetes during pregnancy is responsible for the occurrence of diabetic embryopathy, a spectrum of birth defects that includes heart abnormalities, neural tube defects, and caudal dysgenesis syndromes. Here, we report that mice transgenic for the homeodomain transcription factor Isl-1 develop profound caudal growth defects that resemble human sacral/caudal agenesis. Isl-1 is normally expressed in the pancreas and is required for pancreas development and endocrine cell differentiation. Aberrant regulation of this pancreatic transcription factor causes increased mesodermal cell death, and the severity of defects is dependent on transgene dosage. Together with the finding that mutation of the pancreatic transcription factor HLXB9 causes sacral agenesis, our results implicate pancreatic transcription factors in the pathogenesis of birth defects associated with diabetes.
Samuel C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona, USA.
Yunhua Li
YL
Muller
Yir Gloria
YG
Yueh
Paul J
PJ
Yaworsky
J Michael
JM
Salbaum
Claudia
C
Kappen
D000818:Animals; D017209:Apoptosis; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology* / Q000473:pathology; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009419:Nerve Tissue Proteins; D010641:Phenotype; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000150:complications; D051381:Rats; D013131:Spine / Q000002:abnormalities; D013623:Tail / Q000002:abnormalities / Q000196:embryology; D014157:Transcription Factors
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1