Phenotypes Associated with This Genotype

Genotype
MGI:6402419

• Allelic Composition: Kcnh6^em2Jkya/Kcnh6^em2Jkya
• Genetic Background: involves: C57BL/6N

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

homeostasis/metabolism

abnormal glucose homeostasis ( J:271003 )

• mice exhibit a phenotype changing from hyperinsulinemia to hypoinsulinemia and diabetes

• normal body weight and food intake at all tested ages

• normal insulin sensitivity of peripheral tissues at 3 and 30 weeks of age, as determined by insulin tolerance testing (ITT)

decreased insulin secretion ( J:271003 )

• reduced first- and second-phase insulin secretory responses to glucose during intraperitoneal insulin releasing testing (IPIRT, 3 g glucose/kg bw) at 28 weeks of age

increased fasting circulating glucose level ( J:271003 )

• increased fasting plasma glucose levels at 28 weeks of age relative to age-matched wild-type controls

decreased circulating glucose level ( J:271003 )

• significantly lower random plasma glucose levels in neonatal mice relative to age-matched wild-type controls

decreased circulating insulin level ( J:271003 )

• trend towards lower plasma insulin levels at 28 weeks of age relative to age-matched wild-type controls

increased circulating insulin level ( J:271003 )

• higher plasma insulin levels in neonatal mice relative to age-matched wild-type controls

impaired glucose tolerance ( J:271003 )

• increased blood glucose levels and area under the curve (AUC) during intraperitoneal glucose tolerance testing (IPGTT, 3 g glucose/kg body weight) at 28 weeks of age

• increased blood glucose levels and AUC during IPGTT (2 g glucose/kg body weight) at 24 weeks of age, with low blood glucose levels and lower AUC at 3 weeks of age

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:271003 )

• in primary pancreatic beta cells, the voltage-dependent K⁺ (K_v) channel current is significantly decreased while duration of the action potential is prolonged

decreased insulin secretion ( J:271003 )

• reduced first- and second-phase insulin secretory responses to glucose during intraperitoneal insulin releasing testing (IPIRT, 3 g glucose/kg bw) at 28 weeks of age

nervous system

abnormal action potential ( J:271003 )

• although the magnitude of action potential evoked by a 0.5 nA current is normal, the duration of action potential, esp. the repolarization time, is prolonged in primary pancreatic beta cells

decreased channel response intensity ( J:271003 )

• in primary pancreatic beta cells, the voltage-dependent K⁺ (K_v) channel current is significantly decreased relative to that in wild-type controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
glucose metabolism disease		DOID:4194		J:271003