Phenotypes Associated with This Genotype

Genotype
MGI:3620907

• Allelic Composition: Zmpste24^tm1Sgy/Zmpste24^tm1Sgy
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

A Zmpste24^tm1Sgy/Zmpste24^tm1Sgy mouse.

mortality/aging

premature death ( J:79501 , J:106473 )

• mice die or require euthanasia by 6-7 months of age (J:79501)

skeleton

abnormal long bone morphology ( J:79501 )

abnormal fibula morphology ( J:79501 )

• thinner cortical bone and increased pock marking

abnormal tibia morphology ( J:79501 )

• thinner cortical bone

abnormal axial skeleton morphology ( J:79501 )

abnormal craniofacial bone morphology ( J:79501 )

abnormal cranial suture morphology ( J:79501 , J:95274 )

• the zigzag appearance of cranial sutures is reduced at 2-3 months of age (J:79501)

abnormal zygomatic arch morphology ( J:79501 )

• unhealed fractures result in replacement of the posterior portion of the zygomatic arch with fibrous material containing bone spicules and necrotic debris

• however, at 18 days of age zygomatic arch morphology appears normal

abnormal incisor morphology ( J:95274 )

abnormal lower incisor morphology ( J:79501 )

• at 3 months, lower incisors appear splayed apart, thin and long

long lower incisors ( J:79501 )

• at 3 months

abnormal mandible morphology ( J:95274 )

• osteolytic lesion

micrognathia ( J:79501 )

• at 2 to 3 months but not 18 days

abnormal zygomatic bone morphology ( J:95274 )

abnormal rib morphology ( J:95274 )

rib fractures ( J:79501 )

• by 24-30 weeks, nearly every rib is broken near the costovertebral junction and at the tip

abnormal thoracic vertebrae morphology ( J:79501 )

• bone density is reduced, bodies appear more porous, trabecular bone volume/total bone volume is reduced by 34%, and the thickness of trabeculae is reduced by 36%

kyphosis ( J:79501 )

• at 6-8 weeks of age

abnormal bone structure ( J:79501 )

decreased bone mineral density of presacral vertebrae ( J:79501 )

• bone density is reduced in thoracic vertebrae; however, plasma levels of calcium and phosphate are similar to wild-type and no change in bone turnover rate is detected

decreased compact bone thickness ( J:79501 )

• thinner cortical bone in the tibia and fibula even when corrected for bone size

abnormal trabecular bone morphology ( J:79501 )

• in the thoracic vertebrae trabecular bone volume/total bone volume is reduced by 34%, and the thickness of trabeculae is reduced by 36%

abnormal skeleton physiology ( J:79501 )

fragile skeleton ( J:95274 , J:106473 )

cellular

abnormal cell nucleus morphology ( J:95274 , J:106473 )

• nuclear envelopes contain frequent blebs (J:95274)

• MEFs display blebbing of the nuclear membrane (J:106473)

abnormal cell physiology ( J:79501 )

• striking accumulation of prelamin A in fibroblasts

growth/size/body

abnormal incisor morphology ( J:95274 )

abnormal lower incisor morphology ( J:79501 )

• at 3 months, lower incisors appear splayed apart, thin and long

long lower incisors ( J:79501 )

• at 3 months

cachexia ( J:79501 )

• at 6-8 weeks of age homozygotes appear very malnourished

postnatal growth retardation ( J:79501 , J:95274 , J:106473 )

• weigh slightly less at weaning and gain weight slowly (J:79501)

• severe growth retardation by 4 months of age (J:106473)

behavior/neurological

abnormal grip strength ( J:95274 , J:106473 )

• impaired grip strength by 4 months of age (J:106473)

decreased grip strength ( J:79501 )

• only able to hang from a wire grid for a few seconds

abnormal gait ( J:79501 )

• slow, hobbling gait with frequent dragging of the hindlimbs

homeostasis/metabolism

decreased circulating glucose level ( J:79501 )

• probably secondary to malnutrition

decreased circulating total protein level ( J:79501 )

• probably secondary to malnutrition

muscle

progressive muscle weakness ( J:79501 , J:95274 )

• muscle weakness that worsens with age; however no abnormalities are seen in skeletal muscle fiber morphology (J:79501)

adipose tissue

decreased subcutaneous adipose tissue amount ( J:79501 )

• reduced but present, likely secondary to malnutrition

cardiovascular system

cardiovascular system phenotype ( J:79501 )

N • no heart pathology is seen at any age

liver/biliary system

liver/biliary system phenotype ( J:79501 )

N • no liver pathology is seen at any age

limbs/digits/tail

abnormal fibula morphology ( J:79501 )

• thinner cortical bone and increased pock marking

abnormal tibia morphology ( J:79501 )

• thinner cortical bone

craniofacial

abnormal craniofacial bone morphology ( J:79501 )

abnormal cranial suture morphology ( J:79501 , J:95274 )

• the zigzag appearance of cranial sutures is reduced at 2-3 months of age (J:79501)

abnormal zygomatic arch morphology ( J:79501 )

• unhealed fractures result in replacement of the posterior portion of the zygomatic arch with fibrous material containing bone spicules and necrotic debris

• however, at 18 days of age zygomatic arch morphology appears normal

abnormal incisor morphology ( J:95274 )

abnormal lower incisor morphology ( J:79501 )

• at 3 months, lower incisors appear splayed apart, thin and long

long lower incisors ( J:79501 )

• at 3 months

abnormal mandible morphology ( J:95274 )

• osteolytic lesion

micrognathia ( J:79501 )

• at 2 to 3 months but not 18 days

abnormal zygomatic bone morphology ( J:95274 )

integument

decreased subcutaneous adipose tissue amount ( J:79501 )

• reduced but present, likely secondary to malnutrition

alopecia ( J:79501 )

• at 6-8 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
progeria		DOID:3911	OMIM:176670	J:95274