Mouse Genome Informatics
hm
    Zmpste24tm1Sgy/Zmpste24tm1Sgy
involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

A Zmpste24tm1Sgy/Zmpste24tm1Sgy mouse.

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

skeleton
• thinner cortical bone and increased pock marking
• thinner cortical bone
• the zigzag appearance of cranial sutures is reduced at 2-3 months of age (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
• osteolytic lesion
• at 2 to 3 months but not 18 days
• by 24-30 weeks, nearly every rib is broken near the costovertebral junction and at the tip
• 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%
• at 6-8 weeks of age
• 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
• thinner cortical bone in the tibia and fibula even when corrected for bone size
• in the thoracic vertebrae trabecular bone volume/total bone volume is reduced by 34%, and the thickness of trabeculae is reduced by 36%
• by 24-30 weeks, nearly every rib is broken near the costovertebral junction and at the tip (J:79501)
• bone fractures are also seen in the scapula, clavicle, sternum, zygomatic arch, mandible, and humerus (J:79501)
• fractures are acellular, with little inflammation, minimal healing, and necrotic bone fragments lacking viable osteocytes (J:79501)

cellular
• nuclear envelopes contain frequent blebs (J:95274)
• MEFs display blebbing of the nuclear membrane (J:106473)
• striking accumulation of prelamin A in fibroblasts

growth/size/body
• at 3 months, lower incisors appear splayed apart, thin and long (J:79501)
• at 6-8 weeks of age homozygotes appear very malnourished
• weigh slightly less at weaning and gain weight slowly (J:79501)
• severe growth retardation by 4 months of age (J:106473)

behavior/neurological
• impaired grip strength by 4 months of age (J:106473)
• only able to hang from a wire grid for a few seconds
• slow, hobbling gait with frequent dragging of the hindlimbs

homeostasis/metabolism
• probably secondary to malnutrition
• probably secondary to malnutrition

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

adipose tissue
• reduced but present, likely secondary to malnutrition

cardiovascular system
N
• no heart pathology is seen at any age (J:79501)

liver/biliary system
N
• no liver pathology is seen at any age (J:79501)

limbs/digits/tail
• thinner cortical bone and increased pock marking
• thinner cortical bone

craniofacial
• the zigzag appearance of cranial sutures is reduced at 2-3 months of age (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
• osteolytic lesion
• at 2 to 3 months but not 18 days
• at 3 months, lower incisors appear splayed apart, thin and long (J:79501)

integument
• reduced but present, likely secondary to malnutrition
• at 6-8 weeks of age

Mouse Models of Human Disease
OMIM IDRef(s)
Hutchinson-Gilford Progeria Syndrome; HGPS 176670 J:95274