Phenotypes Associated with This Genotype

Genotype
MGI:2663068

• Allelic Composition: Dach1^tm1Krs/Dach1^tm1Krs
• Genetic Background: involves: 129P2/OlaHsd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

neonatal lethality, complete penetrance ( J:81143 )

• all homozygotes die within 24 hrs after birth in the absence of gross anatomic defects in limbs, spinal cord, eye, and brain

homeostasis/metabolism

cyanosis ( J:81143 )

• homozygotes survive pregnancy but become cyanotic after birth

respiratory system

respiratory distress ( J:81143 )

• newborn homozygotes display irregular and obstructive breathing

behavior/neurological

absent gastric milk in neonates ( J:81143 )

• 11 of 13 newborn homozygotes contain no milk in their stomachs

nervous system

nervous system phenotype ( J:81143 )

N • surprisingly, homozygotes display normal brain morphology, including:

N • no significant alterations in layers I-VI of the cerebral cortex, layers CA1-CA3 of the hippocampus, dentate gyrus, neurocortical neuroepithelium, subventricular zone, cerebellum or brainstem

N • no significant size variations in individual nuclei (paraventricular nucleus, supraoptic nucleus, ventromedial hypothalamic nucleus), and in pituitary

N • normal cell proliferation and distribution of neurons, glia, radial glia, and neuronal progenitors

N • normal distribution and axonal projections in the cortex and hippocampus

N • normal growth kinetics of neural stem cells when cultivated in vitro

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:166952 )

N • at E18.5, one day prior to birth, the pancreas of mutant embryos was normal in size and gross appearance; hematoxylin-eosin staining revealed no obvious morphological discrepancy, and immunofluorescent staining for acinar (Amylase), ductal (Mucin-1) and mesenchymal (Vimentin) markers detected no differences compared to controls

decreased pancreatic beta cell proliferation ( J:166952 )

• staining for Ki-67, a marker of actively proliferating cells, revealed a ~3-fold decrease in the proliferation of insulin-positive cells in mutant embryos at E18.5 compared to controls

• the proliferation of Pdx1-positive pancreatic progenitors at E12.5 is unaffected in the mutants, a result that is consistent with the observation that the overall size of the pancreas was unchanged

decreased pancreatic alpha cell number ( J:166952 )

• at E18.5, a 63% reduction in glucagon-producing alpha-cells is seen in mutant pancreases relative to controls

decreased pancreatic beta cell number ( J:166952 )

• at E18.5, a 67% reduction in the number of insulin-producing beta-cells is seen in mutant pancreases relative to controls

• the remaining beta-cells in the mutant embryos appeared to be fully differentiated, as judged by their expression of Glut2, a characteristic marker of mature beta-cells

small pancreatic islets ( J:166952 )

• at E18.5, endocrine cells are still clustered into islet structures, but the size of the aggregates is reduced in mutants

cellular

decreased pancreatic beta cell proliferation ( J:166952 )

• staining for Ki-67, a marker of actively proliferating cells, revealed a ~3-fold decrease in the proliferation of insulin-positive cells in mutant embryos at E18.5 compared to controls

• the proliferation of Pdx1-positive pancreatic progenitors at E12.5 is unaffected in the mutants, a result that is consistent with the observation that the overall size of the pancreas was unchanged