Phenotypes Associated with This Genotype

Genotype
MGI:4360179

• Allelic Composition: Tg(Cryaa-TAg,Ins2-CALM1)26Ove/0
• Genetic Background: FVB-Tg(Cryaa-TAg,Ins2-CALM1)26Ove

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

cellular

increased mitochondrial size ( J:106851 )

• swollen mitochondria and broken mitochondrial double membranes are observed

• hearts have increased mitochondrial mass, as well as greater area and number

abnormal aerobic respiration ( J:106851 )

• respiratory control ratio (RCR) and state 3 respiration are significantly impaired in mitochondria

cardiovascular system

abnormal heart morphology ( J:106851 )

• hearts have many focal areas of damage with swollen mitochondria, mottled matrix and broken mitochondrial double membranes

increased renal vascular resistance ( J:94602 )

• progressive increase in renal vascular resistance beginning at 3 months of age

hypertension ( J:94602 )

• diastolic blood pressure is elevated in conscious mutants at 3 months of age when measured using a tail-cuff monitor

• by 8 months of age, both diastolic and systolic blood pressure is increased in conscious mutants

• under anesthesia, when measured by intravascular connulation, mutants exhibit a similar blood pressure to anesthetized controls, however this is reduced compared to conscious mutants

homeostasis/metabolism

hyperglycemia ( J:94602 , J:106851 )

• blood glucose levels are more than 2-fold higher than normal by 20 days after birth and continue to rise until at least 60 days of age (J:94602)

decreased circulating serum albumin level ( J:94602 )

• some mutants develop hypoalbuminemia due to excessive loss of albumin

albuminuria ( J:94602 )

• albumin excretion rate increases progressively with age and exceeds 15,000 ug/24 hr at 9 months of age

adipose tissue

decreased body fat mass ( J:94602 )

• loss of fat tissue by 5 months of age

growth/size/body

growth/size/body region phenotype ( J:94602 )

N • mutants exhibit normal weight gain and body weight

decreased body fat mass ( J:94602 )

• loss of fat tissue by 5 months of age

enlarged kidney ( J:94602 )

increased kidney weight ( J:94602 )

• 2-fold increase in kidney weight between 2 and 5 months of age

enlarged liver ( J:94602 )

liver/biliary system

enlarged liver ( J:94602 )

renal/urinary system

increased renal vascular resistance ( J:94602 )

• progressive increase in renal vascular resistance beginning at 3 months of age

albuminuria ( J:94602 )

• albumin excretion rate increases progressively with age and exceeds 15,000 ug/24 hr at 9 months of age

abnormal kidney morphology ( J:94602 )

• kidney shows dilation of the ducts, atrophy of tubular cells, protein casts in the duct lumen, and prominent infiltration of mononuclear cells

enlarged kidney ( J:94602 )

increased kidney weight ( J:94602 )

• 2-fold increase in kidney weight between 2 and 5 months of age

increased renal glomerulus basement membrane thickness ( J:94602 )

• glomeruli exhibit a thickened and irregular basement membrane

abnormal renal glomerulus morphology ( J:94602 )

abnormal glomerular mesangium morphology ( J:94602 )

• expanded mesangium showing enlarged mesangial fraction and mesangial volume, with the greatest rate increase during 2.5-6 months of age

expanded mesangial matrix ( J:94602 )

• diffuse and nodular expansion of mesangial matrix in mutants over 2 months of age

glomerulosclerosis ( J:94602 )

• diffuse and nodular glomerulosclerotic lesions

• nodules are acellular and are similar to Kimmelsteil-Wilson lesions in size

renal glomerulus hypertrophy ( J:94602 )

• glomerular volume is enlarged, with the greatest rate increase during 2.5-6 months of age

hydronephrosis ( J:94602 )

• seen in many mutants over 5 months of age

abnormal renal tubule morphology ( J:94602 )

• expansion of kidney tubules; average cortical tubule cross-sectional area (minus the lumen) is 34% greater in 9 month old mutants than controls

renal fibrosis ( J:94602 )

• significant fibrosis in the kidney by 5 months of age

renal interstitial fibrosis ( J:94602 )

• tubulointerstitial fibrosis

abnormal urinary bladder morphology ( J:94602 )

• many mutants over 5 months of age exhibit bladder stasis

distended urinary bladder ( J:94602 )

• distended bladders are seen in many mutants over 5 months of age

abnormal renal glomerular filtration rate ( J:94602 )

• glomerular filtration rate increases significantly from 2 to 3 months of age but then decreases significantly from 5 to 9 months of age

• decline in glomerular filtration rate coincides with an increase in renal vascular resistance

polyuria ( J:94602 )

• by 2 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:94602