Phenotypes associated with this allele

• Allele Symbol: Rgn^tm1Aish
• Allele Name: targeted mutation 1, Akihito Ishigami
• Allele ID: MGI:2670511
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rgn^tm1Aish/Rgn^tm1Aish	involves: 129P2/OlaHsd * C57BL/6	MGI:2670915
ot2	Rgn^tm1Aish/Y	involves: 129P2/OlaHsd	MGI:5468675
ot3	Rgn^tm1Aish/Y	involves: 129P2/OlaHsd * C57BL/6	MGI:5469321

Genotype
MGI:2670915

hm1

• Allelic Composition: Rgn^tm1Aish/Rgn^tm1Aish
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

liver/biliary system

increased hepatocyte apoptosis ( J:79342 )

♀ • hepatocytes exposed to RNF-alpha and actinomycin D showed a 40% higher level of apoptosis than did cells from wild-type

♀ • caspase-8 activity was doubled

♀ • animals became more susceptible to apoptosis after receiving non-lethal doses of anti-FAS antibody

cellular

increased hepatocyte apoptosis ( J:79342 )

♀ • hepatocytes exposed to RNF-alpha and actinomycin D showed a 40% higher level of apoptosis than did cells from wild-type

♀ • caspase-8 activity was doubled

♀ • animals became more susceptible to apoptosis after receiving non-lethal doses of anti-FAS antibody

homeostasis/metabolism

abnormal vitamin C level ( J:191530 )

♀ • total vitamin C level in lenses is reduced at 16 weeks of age

vision/eye

anterior subcapsular cataract ( J:191530 )

♀ • mice fed a vitamin C-deficient diet and exposed to UVR-B exhibit a greater lens opacity than in controls; location indicates anterior sub-capsular cataract

Genotype
MGI:5468675

ot2

• Allelic Composition: Rgn^tm1Aish/Y
• Genetic Background: involves: 129P2/OlaHsd

Osteogenic disorder in vitamin C-deficient Rgn^tm1Aish/Y mice

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:108295 )

♂ • mice fed a vitamin C-deficient diet at 30 days of age die after 37-135 days on the diet

premature death ( J:88791 )

♂ • males show increased mortality rate after 3 months of age, with a mean survival time of about 6 months of age

♂ • mice show atrophy in almost all abdominal organs upon death

limbs/digits/tail

femur fracture ( J:108295 )

♂ • mice fed a vitamin C-deficient diet beginning at 30 days of age exhibit prominent fracture at the distal end of femurs after 59 days of consuming the diet that is not seen in wild-type mice, indicating the development of scurvy

growth/size/body

decreased body weight ( J:88791 )

♂ • mean body weights of males are about 10%, 15%, and 20% lower than those of wild-type males at 3, 6, and 12 months of age, respectively

weight loss ( J:108295 , J:135721 )

♂ • mice fed a vitamin C-deficient diet at 30 days of age start to lose weight after 25-56 days of the diet which is not seen in wild-type mice (J:108295)

♂ • body weight is lower than wild-type mice at 12 months, but not 6 months, of age (J:135721)

♂ • exposure to cigarette smoke has no effect on body weight (J:135721)

respiratory system

abnormal pulmonary acinus morphology ( J:101810 , J:135721 )

♂ • males exhibit enlargement of the peripheral airspace without alveolar destruction at 1, 2, and 6 months of age compared to control males (J:101810)

♂ • increase in airspace enlargement from 3 to 12 months of age, however no damage or inflammation is seen in the alveoli (J:135721)

emphysema ( J:135721 )

♂ • mice show increased susceptibility to cigarette smoke and develop smoke-induced pulmonary emphysema with marked airspace enlargement and parenchymal destruction

cardiovascular system

abnormal liver vasculature morphology ( J:88791 )

♂ • the central vein in livers is enlarged in diameter with aging

homeostasis/metabolism

abnormal amino acid level ( J:108295 )

♂ • livers and kidneys of mice at the time of death that were fed a vitamin C-deficient diet starting at 30 days of age contain less than 1.6% of the amino acid levels in wild-type livers and kidneys

♂ • mice fed regular chow (containing about 55% mg/kg of vitamin C) for 80 days contain only 6-8% of the amino acid levels in plasma, livers, and kidneys as in wild-type mice, indicating that mutants are vitamin C-deficient

decreased hydroxyproline level ( J:150664 )

♂ • mice fed a vitamin C-deficient diet beginning at 34 days of age for a total of 60, but not 36, days show decreased skin hydroxyproline levels

abnormal circulating amino acid level ( J:108295 )

♂ • mice fed a vitamin C-deficient diet at 30 days of age exhibit a plasma amino acid level less than 1% of that in wild-type mice after 106 days of consuming the diet

increased liver cholesterol level ( J:88791 )

♂ • total hepatic cholesterol level is about 3.3-fold higher than in wild-type livers at 12 months of age

abnormal phospholipid level ( J:88791 )

♂ • total hepatic phospholipid level is about 3.7-fold higher than in wild-type livers

increased liver triglyceride level ( J:88791 )

♂ • total hepatic triglyceride level is about 3.5-fold higher than in wild-type livers at 12 months of age

abnormal vitamin C level ( J:108295 , J:150664 )

♂ • mice fed regular chow (containing about 55% mg/kg of vitamin C) for 80 days are vitamin C-deficient (J:108295)

♂ • mice fed a vitamin C-deficient diet beginning at 34 days of age exhibit skin vitamin C levels to less than 1/50th of wild-type skin after 36 days of the diet and to undetectable levels by 60 days of diet (J:150664)

abnormal enzyme/coenzyme activity ( J:108295 )

♂ • absence of gluconolactase activity in the liver

liver/biliary system

abnormal liver vasculature morphology ( J:88791 )

♂ • the central vein in livers is enlarged in diameter with aging

increased liver cholesterol level ( J:88791 )

♂ • total hepatic cholesterol level is about 3.3-fold higher than in wild-type livers at 12 months of age

increased liver triglyceride level ( J:88791 )

♂ • total hepatic triglyceride level is about 3.5-fold higher than in wild-type livers at 12 months of age

abnormal hepatocyte morphology ( J:88791 )

♂ • hepatocytes from 12 month old mutants contain many large and small empty vacuoles (lipid droplets), enlarged mitochondria with indistinct cristae, large lysosomes filled with electron-dense bodies, and absence of well-developed rough-surfaced endoplasmic reticulum, not seen in wild-type hepatocytes

abnormal hepatocyte mitochondrial morphology ( J:88791 )

• enlarged mitochondria with indistinct cristae

hepatic steatosis ( J:88791 )

♂ • livers show an increase in the size and number of lipid droplets with age indicating lipid droplet storage

cellular

abnormal hepatocyte mitochondrial morphology ( J:88791 )

• enlarged mitochondria with indistinct cristae

increased cellular sensitivity to oxidative stress ( J:135721 )

♂ • mice exposed to cigarette smoke for 8 weeks exhibit an increase in protein carbonyls, malondialdehyde, total glutathione and oxidized glutathione in lung cells compared to wild-type mice

♂ • mice exposed to cigarette smoke for 8 weeks exhibit an increase in apoptosis in bronchial and bronchiolar epithelial cells and alveolar septal cells compared to wild-type controls

oxidative stress ( J:107922 , J:135721 )

♂ • 12 month old mice show increased oxidative stress in the brain as indicated by an increase in the generation of reactive species and NADPH oxidase activity, an increase in oxidatively modified proteins, and infiltration of activated leukocytes (J:107922)

♂ • protein carbonyls are increased in the lungs with age compared to wild-type mice, indicating oxidative stress (J:135721)

♂ • mice exposed to cigarette smoke for 8 weeks exhibit an increase in protein carbonyls, malondialdehyde, total glutathione and oxidized glutathione, and apoptosis of lung cells compared to wild-type mice, indicating increased susceptibility to oxidative stress induced by smoke exposure (J:135721)

nervous system

abnormal brain morphology ( J:107922 )

♂ • 12 month old mice show increased oxidative stress in the brain

♂ • brains of 12 months old mice show infiltration of activated leukocytes, however no neuronal loss or damage is seen in the brain

adipose tissue

decreased percent body fat/body weight ( J:108295 )

♂ • mice fed a vitamin C-deficient diet at 30 days of age exhibit a significant decrease in body fat compared to wild-type mice after 59 days of the diet

behavior/neurological

abnormal gait ( J:108295 )

♂ • mice fed a vitamin C-deficient diet at 30 days of age exhibit an abnormal gait after 31-56 days of the diet which is not seen in wild-type mice

skeleton

femur fracture ( J:108295 )

♂ • mice fed a vitamin C-deficient diet beginning at 30 days of age exhibit prominent fracture at the distal end of femurs after 59 days of consuming the diet that is not seen in wild-type mice, indicating the development of scurvy

rachitic rosary ( J:108295 )

♂ • mice fed a vitamin C-deficient diet beginning at 30 days of age exhibit rachitic rosaries at the junction of costae and costal cartilages after 59 days of consuming the diet that is not seen in wild-type mice, indicating the development of scurvy

decreased bone mineral density ( J:108295 )

♂ • mice fed a vitamin C-deficient diet at 30 days of age exhibit a significant decrease in subcranial total bone mineral density compared to wild-type mice after 59 days of the diet

integument

abnormal hair cycle ( J:150664 )

♂ • mice fed a vitamin C-deficient diet beginning at 34 days of age for a total of 36 days exhibit hair follicles in anagen stage compared to wild-type controls which are in telogen stage, however by 60 days of the vitamin C-deficient diet, hair follicles are back in telogen as in controls

thin dermal layer ( J:150664 )

♂ • mice fed a vitamin C-deficient diet beginning at 34 days of age for a total of 60 days exhibit a thinner dermis than controls

abnormal keratinocyte morphology ( J:150664 )

♂ • mice fed a vitamin C-deficient diet beginning at 34 days of age for a total of 60 days exhibit keratinocytes with flat shapes and many cornified layers remaining on the skin surface compared to wild-type mice

Genotype
MGI:5469321

ot3

• Allelic Composition: Rgn^tm1Aish/Y
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

hearing/vestibular/ear

increased or absent threshold for auditory brainstem response ( J:155625 )

♂ • at 10 months of age, mice fed a vitamin-C deficient diet beginning at 30 days of age, exhibit an increase in auditory brainstem response (ABR) thresholds

♂ • mice fed a vitamin-C sufficient diet exhibit normal ABR thresholds

homeostasis/metabolism

abnormal vitamin C level ( J:155625 , J:191530 )

♂ • vitamin C level in the plasma is lower in mice fed a vitamin-C sufficient diet than in wild-type mice on the same diet (J:155625)

♂ • at 10 months of age, mice fed a vitamin-C deficient diet beginning at 30 days of age, show a reduction in vitamin C levels in the inner ear, plasma, and liver compared to controls on the same diet (J:155625)

♂ • total vitamin C level in the inner ear and liver is normal in mice fed a vitamin-C sufficient diet (J:155625)

♂ • total vitamin C level in lenses is reduced at 16 weeks of age (J:191530)

integument

alopecia ( J:155625 )

♂ • at 10 months of age, mice fed a vitamin-C deficient diet beginning at 30 days of age, exhibit alopecia around the mouth and eyes

nervous system

cochlear ganglion degeneration ( J:155625 )

♂ • at 10 months of age, mice fed a vitamin-C deficient diet beginning at 30 days of age, exhibit a decrease in the number of spiral ganglion cells compared to wild-type mice, indicating degeneration of these cells

♂ • mice fed a vitamin-C sufficient diet exhibit a normal density of spiral ganglion cells

vision/eye

anterior subcapsular cataract ( J:191530 )

♂ • mice fed a vitamin C-deficient diet and exposed to UVR-B exhibit a greater lens opacity than in controls; location indicates anterior sub-capsular cataract