Phenotypes Associated with This Genotype

Genotype
MGI:3618231

• Allelic Composition: Gck^tm1Hrt/Gck⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * DBA

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

cardiovascular system

cardiac fibrosis ( J:250069 )

• mice exhibit cardiac fibrosis, showing increased levels of myocardial collagen which is broken and arranged in a disordered collagen fiber network around the myocardial cells

• treatment with insulin or rosiglitazone decreases collagen and glycoprotein content in the heart

abnormal heart echocardiography feature ( J:250069 )

• echocardiography indicates decreased left ventricle internal dimension during diastole and systole and increased left ventricle posterior wall thickness during diastole and systole in 60 week old mice

• left ventricle internal dimension during diastole is increased after treatment with insulin or rosiglitazone

prolonged PR interval ( J:250069 )

• 60 week old mice exhibit longer PR intervals

• treatment with insulin or rosiglitazone shortens the PR interval

prolonged QRS complex duration ( J:250069 )

• 60 week old mice exhibit longer QRS intervals

• treatment with insulin or rosiglitazone shortens the QRS interval

• however, changes in heart rates, P duration, QT intervals, and corrected QT intervals are not different from wild-type mice

homeostasis/metabolism

increased circulating glucose level ( J:105247 )

• from 2 weeks of age, mice showed increasing blood glucose levels in an age-dependent manner (from 3.8 mmol/L at 2 weeks to 8.9 mmol/L at 6 weeks); level at 6 weeks is significantly higher than control level (5.3 mmol/L)

increased fasting circulating glucose level ( J:250069 )

• fasting glucose levels are increased

• treatment with rosiglitazone does not change fasting glucose levels

impaired glucose tolerance ( J:105247 , J:250069 )

• mice display glucose intolerance (J:105247)

• glucose levels at 0, 30, 60, and 120 minutes after glucose injection are higher (J:250069)

• treatment with rosiglitazone decreases the impairment in the glucose tolerance response at the 60 and 120 minute time points (J:250069)

insulin resistance ( J:250069 )

• homeostasis model assessment of insulin resistance (HOMA-IR) levels are increased

• treatment with rosiglitazone results in a decrease in HOMA-IR levels

cellular

abnormal mitochondrial crista morphology ( J:250069 )

• cristae density of the mitochondria is decreased in the myocardium

increased mitochondrial number ( J:250069 )

• mitochondrial volume density and number are increased in the myocardium

• treatment with insulin or rosiglitazone restores these properties to normal levels

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:250069 )

• the homeostasis model assessment of beta-cell function (HOMA-Beta-cell) levels are decreased

• treatment with rosiglitazone does not change HOMA-Beta-cell levels

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young type 2		DOID:0111100	OMIM:125851	J:105247 , J:250069