Phenotypes Associated with This Genotype

Genotype
MGI:2181617

• Allelic Composition: Kl^kl/Kl^kl
• Genetic Background: either: C.Cg-Kl^kl or (involves: C3H/HeJ * C57BL/6J)

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

cellular

azoospermia ( J:44109 )

♂

mortality/aging

premature death ( J:44109 )

• average lifespan is 60.7 days with none surviving more than 100 days

premature aging ( J:44109 )

• overall phenotype resembles changes seen in human aging

growth/size/body

postnatal growth retardation ( J:44109 )

• beginning around 3-4 weeks of age

respiratory system

calcified pulmonary alveolus ( J:44109 )

• ectopic calcification of the alveolar cells

emphysema ( J:44109 )

• however, arterial blood oxygen content is similar to controls

cardiovascular system

arteriosclerosis ( J:44109 )

• progressive arteriosclerosis beginning around 4 weeks of age

calcified artery ( J:44109 )

• mid-sized muscular arteries show medial calcification and intimal thickening

• small arteries in the kidney are extensively calcified

calcified aorta ( J:44109 )

• extensive medial calcification in the aorta

abnormal blood circulation ( J:44109 )

• circulation slows beginning around 3-4 weeks of age

skeleton

kyphosis ( J:44109 )

abnormal bone structure ( J:44109 )

decreased osteoclast cell number ( J:44109 )

• reduced numbers

decreased bone mineral density ( J:44109 )

• decreased bone mineral density particularly in the mid portion of the long bones where density is reduced by about 20% compared to controls

decreased compact bone thickness ( J:44109 )

osteoporosis ( J:44109 )

• resembles human senile osteoporosis

abnormal bone ossification ( J:44109 )

behavior/neurological

short stride length ( J:44109 )

• base length corrected mean stride lengths are reduced

decreased locomotor activity ( J:44109 )

• become inactive starting around 3-4 weeks of age

• mice older than 6 weeks of age display about a 50% reduction in spontaneous activit

reproductive system

absent mature ovarian follicles ( J:44109 )

♀

ovary atrophy ( J:44109 )

♀

abnormal seminiferous tubule morphology ( J:44109 )

♂ • extremely atrophic

testicular atrophy ( J:44109 )

♂

vulva atrophy ( J:44109 )

♀ • external female genitalia are atrophic

uterus atrophy ( J:44109 )

♀

abnormal gametogenesis ( J:44109 )

• impaired maturation

azoospermia ( J:44109 )

♂

arrest of male meiosis ( J:44109 )

♂ • fail to mature beyond the pachytene stage

external male genitalia atrophy ( J:44109 )

♂ • external male genitalia are atrophic

infertility ( J:44109 )

• males and females are unable to mate

nervous system

abnormal adenohypophysis morphology ( J:44109 )

abnormal gonadotroph morphology ( J:44109 )

• luteinizing hormone and follicle stimulating hormone producing cells appear slightly atrophic

decreased somatotroph cell size ( J:44109 )

• growth hormone producing cells are smaller

decreased somatotroph secretory granule number ( J:44109 )

• the number of secretory granules in growth hormone producing cells is reduced

Purkinje cell degeneration ( J:44109 )

• however, no other signs of brain atrophy or age-related changes in the brain are detected

decreased Purkinje cell number ( J:44109 )

endocrine/exocrine glands

abnormal adenohypophysis morphology ( J:44109 )

abnormal gonadotroph morphology ( J:44109 )

• luteinizing hormone and follicle stimulating hormone producing cells appear slightly atrophic

decreased somatotroph cell size ( J:44109 )

• growth hormone producing cells are smaller

decreased somatotroph secretory granule number ( J:44109 )

• the number of secretory granules in growth hormone producing cells is reduced

thymus atrophy ( J:44109 )

• thymus is barely detectable at 6-9 weeks of age but appears normal at early development stages

absent mature ovarian follicles ( J:44109 )

♀

ovary atrophy ( J:44109 )

♀

abnormal seminiferous tubule morphology ( J:44109 )

♂ • extremely atrophic

testicular atrophy ( J:44109 )

♂

decreased insulin secretion ( J:44109 )

• decrease in pancreatic insulin level

immune system

thymus atrophy ( J:44109 )

• thymus is barely detectable at 6-9 weeks of age but appears normal at early development stages

abnormal leukocyte cell number ( J:44109 )

• ratio of lymphocytes to leukocytes is decreased in the peripheral blood, 34.5 +/- 7.6% compared to 61.3 +/- 14.1% in controls

decreased osteoclast cell number ( J:44109 )

• reduced numbers

homeostasis/metabolism

decreased insulin secretion ( J:44109 )

• decrease in pancreatic insulin level

hypoglycemia ( J:44109 )

• levels are 115.8 +/- 13.8 mg/dl compared to 231.5 +/- 22.6 mg/dl in controls

abnormal circulating mineral level ( J:44109 )

• slight increase in phosphorus level

increased circulating calcium level ( J:44109 )

• slight

calcinosis ( J:44109 )

• ectopic calcification of the arterial walls, stomach, bronchial mucosa, alveolar cells, choroid plexus, skin, testes, and cardiac muscle

adipose tissue

decreased subcutaneous adipose tissue amount ( J:44109 )

• barely detectable

muscle

calcified muscle ( J:44109 )

• calcification of the cardiac muscle

hematopoietic system

thymus atrophy ( J:44109 )

• thymus is barely detectable at 6-9 weeks of age but appears normal at early development stages

abnormal leukocyte cell number ( J:44109 )

• ratio of lymphocytes to leukocytes is decreased in the peripheral blood, 34.5 +/- 7.6% compared to 61.3 +/- 14.1% in controls

decreased osteoclast cell number ( J:44109 )

• reduced numbers

integument

decreased subcutaneous adipose tissue amount ( J:44109 )

• barely detectable

sparse hair ( J:44109 )

decreased hair follicle number ( J:44109 )

thin epidermis ( J:44109 )

abnormal skin condition ( J:44109 )

• overall atrophy resembling senile atrophoderma in humans

calcified skin ( J:44109 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pulmonary emphysema		DOID:9675	OMIM:130700	J:44109