Phenotypes Associated with This Genotype

Genotype
MGI:5308379

• Allelic Composition: Tg(RP3-340H11)29Kel/0
• Genetic Background: involves: C57BL/6J * CBA/Ca

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

cellular

paternal imprinting ( J:91709 )

homeostasis/metabolism

increased insulin secretion ( J:91709 )

• in vitro insulin secretion by overnight-cultured islets in response to 0.1 uM pituitary adenylate cyclase-activating polypeptide (PACAP) at 17 mM glucose is significantly greater for islets of transgenic than of control 2-8 day old mice

• islets from transgenic and littermate control mice of all age groups exhibit no difference in insulin secretion at 3 mM or 17 mM glucose alone

hyperglycemia ( J:91709 )

• 2-8 day old transgenic mice have significantly elevated blood glucose concentrations only when the transgene is paternally inherited; the hyperglycemia does not persist in juvenile (1.5-2 months) or adult (6-10 months) mice

• when the transgene is maternally inherited, blood glucose concentration does not differ between transgenic progeny and their wild-type littermates at any life stage

impaired glucose tolerance ( J:91709 )

• 2-8 day old and 6-10 month old, but not 1.5-2 month old transgenic mice exhibit reduced glucose tolerance following intraperitoneal glucose challenge

• serum insulin levels 30 minutes after intraperitoneal glucose challenge are lower in 6-10 month old, though not in 2-8 day old or 1.5-2 month old transgenic mice than in age-matched controls

increased insulin sensitivity ( J:91709 )

• 6-10 month old transgenic mice exhibit an abnormally rapid return to higher blood glucose levels, within 45 minutes, following insulin challenge

• 2-8 day old and 1.5-2 month old transgenic mice, however, have a normal response to insulin challenge

• euglycemic insulinemic clamps demonstrate identical insulin sensitivity of 6-10 month old transgenic and wild-type adults

endocrine/exocrine glands

decreased PP cell number ( J:91709 )

• at embryonic day 14.5 dpc, pancreatic peptide- (PP-) positive structures are present at lower total volume density in pancreata of transgenic than of wild-type embryos

decreased pancreatic alpha cell number ( J:91709 )

• at embryonic day 14.5 dpc, glucagon-positive structures are present at lower total volume density in pancreata of transgenic than of wild-type embryos

increased pancreatic alpha cell number ( J:91709 )

• immunohistochemical anaysis of pancreata from 1.5-2 month old transgenic and wild-type mice reveals a significantly greater density of glucagon-positive structures in the former

decreased pancreatic beta cell mass ( J:91709 )

• at 14.5 dpc, insulin-positive structures are present at lower total volume density in pancreata of transgenic than of wild-type embryos

• immunohistochemical anaysis of pancreata from 2-8 day old and from 6-10 month old transgenic and wild-type mice showed no differences in the intensity of anti-insulin staining or in the size or density of insulin-positive structures

decreased pancreatic beta cell number ( J:91709 )

• at 14.5 dpc, insulin-positive structures are present at lower total volume density in pancreata of transgenic than of wild-type embryos

• immunohistochemical anaysis of pancreata from 2-8 day old and from 6-10 month old transgenic and wild-type mice showed no differences in the intensity of anti-insulin staining or in the size or density of insulin-positive structures

increased pancreatic beta cell number ( J:91709 )

• immunohistochemical anaysis of pancreata from 1.5-2 month old transgenic and wild-type mice reveals a significantly greater total mass of insulin-positive structures, without increased cell size, in the former

• immunohistochemical anaysis of pancreata from 2-8 day old and from 6-10 month old transgenic and wild-type mice showed no differences in the intensity of anti-insulin staining or in the size or density of insulin-positive structures

decreased pancreatic delta cell number ( J:91709 )

• at embryonic day 14.5 dpc, somatostatin-positive structures are present at lower total volume density in pancreata of transgenic than of wild-type embryos

abnormal pancreas development ( J:91709 )

• development of the exocrine pancreas - the islets and their component alpha, beta, delta and PP cells - is delayed in transgenic embryos; at embryonic day 14.5 dpc, the numbers and/or total masses of these cell types are significantly lower than in control embryos

• pancreas/body weight ratios are similar in transgenic and wild-type mice at all postnatal stages

abnormal pancreatic beta cell physiology ( J:91709 )

• total pancreatic insulin content is significantly lower in 2-8 day old transgenic than in control mice

• however, neither mean serum insulin levels of 2-8 day old nor fasted insulin levels of 1.5-2 month old or 6-10 month old transgenic mice differ from those of their age-matched controls

increased insulin secretion ( J:91709 )

• in vitro insulin secretion by overnight-cultured islets in response to 0.1 uM pituitary adenylate cyclase-activating polypeptide (PACAP) at 17 mM glucose is significantly greater for islets of transgenic than of control 2-8 day old mice

• islets from transgenic and littermate control mice of all age groups exhibit no difference in insulin secretion at 3 mM or 17 mM glucose alone

growth/size/body

growth/size/body region phenotype ( J:91709 )

N • unlike human infants with TNDM1, very young (2-8 day old) mice with this transgene do not weigh less than their wild-type littermates; the postnatal growth kinetics of transgenic and wild-type mice also are similar

digestive/alimentary system

digestive/alimentary phenotype ( J:91709 )

N • 2-8 day old mice with this transgene do not exhibit macroglossia, as do human infants with TNDM1

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
transient neonatal diabetes mellitus		DOID:0060334	OMIM:601410 OMIM:610374 OMIM:610582	J:91709