Phenotypes Associated with This Genotype

Genotype
MGI:3846426

• Allelic Composition: Cisd2^tm1Tfts/Cisd2^tm1Tfts
• Genetic Background: B6.129S7-Cisd2^tm1Tfts

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

mortality/aging

premature death ( J:148467 )

• median life span is 67 weeks compared with 109 weeks for wild-type mice

premature aging ( J:148467 )

• starting at 8 weeks of age, mice exhibit signs of premature aging including prominent eyes and ears, cataracts, blindness, early depigmentation of fur, decreased hair density, thickened epidermis, decreased subcutaneous adipose, thin femur trabecular, reduced respiratory parameters, and muscle degeneration

• however, mouse embryonic fibroblasts exhibit normal proliferation and the apoptosis rates of brain, skeletal muscle, and cardiac muscle cells are normal

skeleton

lordokyphosis ( J:148467 )

• by 12 weeks, mice exhibit lordokyphosis

decreased bone mineral density of femur ( J:148467 )

• decreased bone mineral density after 8 weeks and progressively more severe at 24 weeks in the femur

decreased trabecular bone thickness ( J:148467 )

• after 12 weeks

growth/size/body

prominent ears ( J:148467 )

• at 8 weeks, mice exhibit prominent ears compared with wild-type mice

decreased body mass index ( J:148467 )

• after 12 weeks

small thoracic cavity ( J:148467 )

• after 12 weeks, mice exhibit a decrease in thoracic volume compared with wild-type mice

decreased body size ( J:148467 )

decreased body weight ( J:148467 )

• 13% reduction at 4 wk, 27% reduction at 8 wk, 41% reduction at 36 wk

postnatal growth retardation ( J:148467 )

• mice exhibit almost no growth after 5 weeks

nervous system

abnormal optic nerve morphology ( J:148467 )

• mice exhibit progressive neurodegeneration which includes optic nerve defects

neurodegeneration ( J:148467 )

• mice exhibit progressive neurodegeneration which includes optic nerve defects

axon degeneration ( J:148467 )

• at 2 weeks

demyelination ( J:148467 )

• myelin sheath disintegrate at 2 weeks

homeostasis/metabolism

decreased oxygen consumption ( J:148467 )

• stimulated skeletal muscle mitochondria exhibit reduced oxygen consumption and respiratory control ratio compared with wild-type mitochondria

abnormal glucose homeostasis ( J:148467 )

• mice exhibit impaired glucose homeostasis due to abnormal insulin secretion rather than insulin resistance

decreased insulin secretion ( J:148467 )

impaired glucose tolerance ( J:148467 )

increased insulin sensitivity ( J:148467 )

respiratory system

decreased tidal volume ( J:148467 )

abnormal respiratory function ( J:148467 )

• after 12 weeks of age, mice exhibit reduced respiratory parameters compared to with wild-type mice

vision/eye

retina neovascularization ( J:148467 )

abnormal optic nerve morphology ( J:148467 )

• mice exhibit progressive neurodegeneration which includes optic nerve defects

corneal opacity ( J:148467 )

• at 20 weeks, mice exhibit opacity of the cornea without cataracts formation

exophthalmos ( J:148467 )

• at 8 weeks, mice exhibit prominent eyes compared with wild-type mice

blindness ( J:148467 )

• at 20 weeks

muscle

abnormal myocardium layer morphology ( J:148467 )

• by 3 weeks

abnormal muscle fiber morphology ( J:148467 )

• mice exhibit angular fibers unlike in wild-type mice

muscle degeneration ( J:148467 )

• at 3 weeks, mice exhibit progressive muscle degeneration unlike wild-type mice

adipose tissue

decreased subcutaneous adipose tissue amount ( J:148467 )

• at 48 weeks

decreased total body fat amount ( J:148467 )

• 50% reduction at 52 wk, 80% reduction at 80 wk

behavior/neurological

decreased fluid intake ( J:148467 )

• at 12 to 14 weeks

decreased food intake ( J:148467 )

• at 12 to 14 weeks

cardiovascular system

retina neovascularization ( J:148467 )

abnormal myocardium layer morphology ( J:148467 )

• by 3 weeks

cellular

abnormal mitochondrial morphology ( J:148467 )

• at 2 weeks, mice exhibit mitochondrial degeneration in axons of the sciatic nerve, brain cells, cardiac muscle cells, and skeletal muscle cells unlike wild-type mice

abnormal respiratory electron transport chain ( J:148467 )

• mitochondria exhibit a 30% reduction in electron transport activities of complexes I-III, II-III, and IV compared with wild-type mitochondria

• however, the production of reactive oxygen species is normal

digestive/alimentary system

abnormal defecation ( J:148467 )

• at 12 to 14 weeks, mice exhibit decreased stool production compared with wild-type mice

endocrine/exocrine glands

decreased insulin secretion ( J:148467 )

hearing/vestibular/ear

prominent ears ( J:148467 )

• at 8 weeks, mice exhibit prominent ears compared with wild-type mice

pigmentation

abnormal coat/hair pigmentation ( J:148467 )

• at 48 weeks, mice exhibit premature fur depigmentation

renal/urinary system

oliguria ( J:148467 )

• at 12 to 14 weeks

craniofacial

prominent ears ( J:148467 )

• at 8 weeks, mice exhibit prominent ears compared with wild-type mice

integument

decreased subcutaneous adipose tissue amount ( J:148467 )

• at 48 weeks

abnormal coat/hair pigmentation ( J:148467 )

• at 48 weeks, mice exhibit premature fur depigmentation

decreased hair follicle number ( J:148467 )

• at 48 weeks, mice exhibit hair follicle atrophy, decrease hair density, and decreased hair regrowth rate compared with wild-type mice

thick epidermis ( J:148467 )

• at 48 weeks, the epidermis is thickened and the surface is expanded with atrophy unlike in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Wolfram syndrome 2		DOID:0110630	OMIM:604928	J:148467