Phenotypes Associated with This Genotype

Genotype
MGI:3623587

• Allelic Composition: Hells^tm1Rarc/Hells^tm1Rarc
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

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

mortality/aging

perinatal lethality, incomplete penetrance ( J:107145 )

• slightly fewer than expected homozygotes are found at birth (about 20.5% versus 25% expected) and about 60% die shortly after or within a few days of birth

postnatal lethality, incomplete penetrance ( J:107145 )

• about 60% die shortly after or within a few days of birth while the remaining 40% survive up to several weeks

premature aging ( J:107145 )

• at P15 homozygotes show signs of premature aging including, graying hair, balding, reduced fat deposition, unstable gait, cachexia, and kyphosis

respiratory system

atelectasis ( J:107145 )

• many newborn homozygotes display diffuse alveolar atelectasis

respiratory failure ( J:107145 )

• many newborn homozygotes display lack of aeration of the smaller airways suggesting respiratory failure; however, expression of surfactants is similar to wild-type mice

homeostasis/metabolism

hypoglycemia ( J:107145 )

• at P0 and P15 serum glucose levels are 52% and 50% less than wild-type mice, despite the presence of milk in homozygotes' stomachs

skeleton

abnormal long bone morphology ( J:107145 )

short femur ( J:107145 )

• short femur with reduced bone mineral density and smaller epiphysis

abnormal tibia morphology ( J:107145 )

• cortical and trabecular bone volume are decreased

short tibia ( J:107145 )

• short tibia with reduced bone mineral density and smaller epiphysis

abnormal long bone epiphysis morphology ( J:107145 )

• smaller femur and tibia epiphyses

abnormal axial skeleton morphology ( J:107145 )

abnormal thoracic vertebrae morphology ( J:107145 )

• cortical and trabecular bone volume are decreased in thoracic vertebral bodies

kyphosis ( J:107145 )

• seen by P15

decreased bone mineral density ( J:107145 )

osteoporosis ( J:107145 )

delayed bone ossification ( J:107145 )

• delayed bone development

delayed endochondral bone ossification ( J:107145 )

• mostly calcified cartilage rather than trabecular bone is present at P15

immune system

small thymus ( J:107145 )

• by 2 weeks of age the thymus is moderately smaller

thymus hypoplasia ( J:107145 )

• by 2 weeks of age severe lymphoid depletion is seen particularly in the cortex

• at P14 thymus cell proliferation is significantly decreased compared to wild-type mice

cellular

abnormal chromosome number ( J:107145 )

• by passage 10 an increased proportion of homozygous MEFs have an abnormally high DNA content and increased chromosomal number; however no significant difference in DNA content or chromosome number is seen in the thymus or bone marrow

decreased cellular sensitivity to gamma-irradiation ( J:107145 )

• consistent with early senescence phenotype

decreased cell proliferation ( J:107145 )

• MEFs display early onset senescence and decreased proliferative capacity after passage 6; however, no defect in passage through the the cell cycle is detected

renal/urinary system

abnormal kidney morphology ( J:107145 )

• epithelial attenuation and accumulation of eosinophilic intracytoplasmic inclusions are seen at 2 weeks of age

small kidney ( J:107145 )

• by 2 weeks of age the kidneys are slightly smaller

abnormal renal tubule morphology ( J:107145 )

• tubular degeneration is seen at 2 weeks of age

dilated renal tubule ( J:107145 )

• at 2 weeks of age

growth/size/body

decreased embryo weight ( J:107145 )

• a decrease in homozygote body weight compared to wild-type mice is first detected at E12.5 and this difference is increased at E15.5 and P0

decreased birth weight ( J:107145 )

• at P0 homozygotes weigh 25% less than wild-type mice

decreased body weight ( J:107145 )

• by 2 weeks of age homozygotes weigh 70% less than wild-type mice

cachexia ( J:107145 )

• seen by P15

decreased fetal weight ( J:107145 )

• reduction in homozygote body weight is increased at E15.5

behavior/neurological

abnormal gait ( J:107145 )

• unstable gait

adipose tissue

decreased subcutaneous adipose tissue amount ( J:107145 )

• by P14 nearly complete loss of the subcutaneous adipose tissue is seen

pigmentation

abnormal coat/hair pigmentation ( J:107145 )

• graying is seen by P15

limbs/digits/tail

short femur ( J:107145 )

• short femur with reduced bone mineral density and smaller epiphysis

abnormal tibia morphology ( J:107145 )

• cortical and trabecular bone volume are decreased

short tibia ( J:107145 )

• short tibia with reduced bone mineral density and smaller epiphysis

embryo

decreased embryo weight ( J:107145 )

• a decrease in homozygote body weight compared to wild-type mice is first detected at E12.5 and this difference is increased at E15.5 and P0

hematopoietic system

small thymus ( J:107145 )

• by 2 weeks of age the thymus is moderately smaller

thymus hypoplasia ( J:107145 )

• by 2 weeks of age severe lymphoid depletion is seen particularly in the cortex

• at P14 thymus cell proliferation is significantly decreased compared to wild-type mice

integument

decreased subcutaneous adipose tissue amount ( J:107145 )

• by P14 nearly complete loss of the subcutaneous adipose tissue is seen

abnormal coat/hair pigmentation ( J:107145 )

• graying is seen by P15

alopecia ( J:107145 )

• balding by P15

hyperkeratosis ( J:107145 )

• hyperkeratosis of the epidermis is seen by P14

endocrine/exocrine glands

small thymus ( J:107145 )

• by 2 weeks of age the thymus is moderately smaller

thymus hypoplasia ( J:107145 )

• by 2 weeks of age severe lymphoid depletion is seen particularly in the cortex

• at P14 thymus cell proliferation is significantly decreased compared to wild-type mice