Phenotypes Associated with This Genotype

Genotype
MGI:3621007

• Allelic Composition: Zmpste24^tm1Otin/Zmpste24^tm1Otin
• Genetic Background: involves: 129P2/Ola * C57BL/6

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

cellular

cardiac interstitial fibrosis ( J:76209 )

• in mutants, fibrosis is seen along with infiltration of inflammatory cells

increased hair follicle apoptosis ( J:76209 )

• at 16 weeks, there is an increase in the number of apoptotic bodies in hair follicles

mortality/aging

premature death ( J:76209 )

• most nulls die by the age of 20 weeks

growth/size/body

increased heart weight ( J:76209 )

• mutants dissected between 14 and 20 weeks of age exhibit greater heart weights compared to wild-type

abnormal body weight ( J:76209 )

• at 7 weeks of age, nulls have gained 40% less weight than littermates

decreased body size ( J:76209 )

• at 7 weeks of age, nulls are 30% smaller than wild-type or heterozygous littemates

weight loss ( J:76209 )

• by 2 months of age, homozygotes begin to progressively lose weight

postnatal growth retardation ( J:76209 )

• by 4 to 6 weeks after birth, growth rate of homzygotes is reduced; by 7 weeks of age, mutants stop growing

increased kidney weight ( J:76209 )

• mutants have increased kidney weights compared to controls between 14 and 20 weeks of age

behavior/neurological

abnormal postural reflex ( J:76209 )

• when lifted by their tails, mice reflexively overextend their hindlimbs and cannot bow upwards like wild-type mice

tremors ( J:76209 )

• mice exhibit tremors when lifted by their tails

hunched posture ( J:76209 )

• at 2 months of age, mice display a hunched posture

abnormal locomotor behavior ( J:76209 )

• nulls become less mobile, and slap and splay hindpaws while walking

cardiovascular system

increased heart weight ( J:76209 )

• mutants dissected between 14 and 20 weeks of age exhibit greater heart weights compared to wild-type

dilated heart left ventricle ( J:76209 )

• some mutants display dilation of the left ventricle

thin ventricular wall ( J:76209 )

• significant thinning of the ventricular wall is observed

dilated heart right ventricle ( J:76209 )

• some mutants display dilation of the right ventricle

cardiac interstitial fibrosis ( J:76209 )

• in mutants, fibrosis is seen along with infiltration of inflammatory cells

dilated cardiomyopathy ( J:76209 )

homeostasis/metabolism

increased circulating aspartate transaminase level ( J:76209 )

• in end-stage mutant mice (approximately 20 weeks of age), a significant rise in serum levels of aspartate aminotransferase is seen

increased circulating creatine kinase level ( J:76209 )

• in end-stage mutant mice (approximately 20 weeks of age), a significant rise in serum levels of creatine kinase is seen

increased circulating glutamate dehydrogenase level ( J:76209 )

• in end-stage mutant mice (approximately 20 weeks of age), a significant rise in serum levels of glutamate dehydrogenase is seen

muscle

dilated cardiomyopathy ( J:76209 )

dystrophic muscle ( J:76209 )

• fibers of the paravertebral region, deltoid and quadriceps are dystrophic

renal/urinary system

increased kidney weight ( J:76209 )

• mutants have increased kidney weights compared to controls between 14 and 20 weeks of age

limbs/digits/tail

abnormal femur morphology ( J:76209 )

• in mutants there is growth plate dysplasia in the distal femur

abnormal tibia morphology ( J:76209 )

• in mutants there is growth plate dysplasia in the proximal tibia

adipose tissue

absent subcutaneous adipose tissue ( J:76209 )

• at 16 weeks of age, mutants have lost the subcutaneous fat layer

immune system

abnormal thymus corticomedullary boundary morphology ( J:76209 )

• young mice display loss of corticomedullary demarcation

thymus hypoplasia ( J:76209 )

• young mice display thymic hypoplasia with loss of corticomedullary demarcation

skeleton

abnormal femur morphology ( J:76209 )

• in mutants there is growth plate dysplasia in the distal femur

abnormal tibia morphology ( J:76209 )

• in mutants there is growth plate dysplasia in the proximal tibia

scoliosis ( J:76209 )

• mice display scoliosis by 2 months of age

hematopoietic system

abnormal thymus corticomedullary boundary morphology ( J:76209 )

• young mice display loss of corticomedullary demarcation

thymus hypoplasia ( J:76209 )

• young mice display thymic hypoplasia with loss of corticomedullary demarcation

integument

absent subcutaneous adipose tissue ( J:76209 )

• at 16 weeks of age, mutants have lost the subcutaneous fat layer

increased hair follicle apoptosis ( J:76209 )

• at 16 weeks, there is an increase in the number of apoptotic bodies in hair follicles

premature hair loss ( J:76209 )

• one third of mice over 16 weeks of age begin to lose their fur, whiskers and sometimes eyelashes

abnormal hair follicle morphology ( J:76209 )

• hair follicles are atrophic in mutants at 16 weeks

epidermal atrophy ( J:76209 )

• at 16 weeks of age, epidermis is atrophic with an increase in the number of apoptotic bodies in the basal layer

endocrine/exocrine glands

abnormal thymus corticomedullary boundary morphology ( J:76209 )

• young mice display loss of corticomedullary demarcation

thymus hypoplasia ( J:76209 )

• young mice display thymic hypoplasia with loss of corticomedullary demarcation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Emery-Dreifuss muscular dystrophy		DOID:11726	OMIM:PS310300	J:76209
familial partial lipodystrophy		DOID:0050440	OMIM:PS151660	J:76209