Phenotypes associated with this allele
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Zmpste24tm1Sgy mutation
(2 available);
any
Zmpste24 mutation
(32 available)
|
|
|
mortality/aging
|
|
• treatment with an FTI increased the survival of both male and female mutants significantly compared with vehicle-treated mutant controls; by 20 weeks of age, 6 of 14 vehicle-treated mutants had died, but only 1 of 13 FTI-treated mutants was dead
|
growth/size/body
|
|
• male and female mutant mice treated with an FTI gain more weight than vehicle treated controls
|
skeleton
|
|
• at 20 weeks, the median number of rib fractures in FTO-treated mice is 2, compared to 14 in vehicle treated mice
|
behavior/neurological
|
|
• 100% of male and female mutant mice receiving vehicle exhibit abnormal grip strength by 16 weeks of age; only 28% of female and 33% of male mutants receiving a farnesyltransferase inhibitor (FTI) show a grip abnormality in a grid-hang test
• the delay in appearance of grip abnormalities is significant for male and female mutants
• the mean length of hang time of inhibitor-treated mice is longer than for vehicle treated mice
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Zmpste24tm1Sgy mutation
(2 available);
any
Zmpste24 mutation
(32 available)
|
|
|
mortality/aging
skeleton
growth/size/body
|
|
• far smaller than wild-type mice
(J:160705)
|
behavior/neurological
|
|
• invariably die from severe, progressive inanition
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Zmpste24tm1Sgy mutation
(2 available);
any
Zmpste24 mutation
(32 available)
|
|
|
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
|
|
|
• 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
|
|
|
• at 3 months, lower incisors appear splayed apart, thin and long
|
|
|
• 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%
|
|
|
• 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%
|
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
|
|
|
• 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
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
|
liver/biliary system
|
N |
• no liver pathology is seen at any age
|
limbs/digits/tail
|
|
• thinner cortical bone and increased pock marking
|
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
|
|
|
• at 3 months, lower incisors appear splayed apart, thin and long
|
|
|
• at 2 to 3 months but not 18 days
|
integument
|
|
• reduced but present, likely secondary to malnutrition
|
Allelic
Composition |
Zmpste24tm1Sgy/Zmpste24+
|
|
Genetic
Background |
involves: 129S4/SvJae * C57BL/6 |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Zmpste24tm1Sgy mutation
(2 available);
any
Zmpste24 mutation
(32 available)
|
|
|
skeleton
|
|
• at 15 months of age in 2 of 2 heterozygotes degraded transverse and spinous processes are seen
|
|
|
• at 15 months of age in 2 of 2 heterozygotes degraded transverse and spinous processes are seen
|
growth/size/body
|
|
• seen in older heterozygotes (around 15 months of age)
|
behavior/neurological
|
|
• appear weak at 15 months of age
|
integument
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm6Lgf mutation
(0 available);
any
Lmna mutation
(82 available)
Zmpste24tm1Sgy mutation
(2 available);
any
Zmpste24 mutation
(32 available)
|
|
|
digestive/alimentary system
|
N |
• mice do not exhibit intestinal abnormalities
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm10Lgf mutation
(0 available);
any
Lmna mutation
(82 available)
Zmpste24tm1Sgy mutation
(2 available);
any
Zmpste24 mutation
(32 available)
|
|
|
digestive/alimentary system
|
|
• esophagus shows a cornified squamous epithelium
|
|
|
• mice develop dilated, yellow esophagus
|
|
|
• thinning and fibrosis of the muscularis externa, pathology similar to achalasia
|
muscle
|
|
• thinning and fibrosis of the muscularis externa, pathology similar to achalasia
|
nervous system
|
N |
• mice show no pathology in the central nervous system
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm6Lgf mutation
(0 available);
any
Lmna mutation
(82 available)
Zmpste24tm1Sgy mutation
(2 available);
any
Zmpste24 mutation
(32 available)
|
|
|
mortality/aging
|
|
• survival is worse than in Zmpste24 single mutants
|
|
|
• survival is worse than in Zmpste24 single mutants
|
growth/size/body
|
|
• smaller than Zmpste24 single mutants
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm6Lgf mutation
(0 available);
any
Lmna mutation
(82 available)
Zmpste24tm1Sgy mutation
(2 available);
any
Zmpste24 mutation
(32 available)
|
|
|
mortality/aging
|
|
• survival is worse than in Zmpste24 single mutants
|
|
|
• survival is worse than in Zmpste24 single mutants
|
growth/size/body
|
|
• smaller than Zmpste24 single mutants
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm7Lgf mutation
(0 available);
any
Lmna mutation
(82 available)
Zmpste24tm1Sgy mutation
(2 available);
any
Zmpste24 mutation
(32 available)
|
|
|
mortality/aging
|
N |
• mice exhibit normal survival
|
skeleton
|
|
• compared to in Zmpste24tm1Sgy homozygotes
|
growth/size/body
mortality/aging
|
|
• die by 4-6 weeks of age
|
growth/size/body
muscle
mortality/aging
|
|
• die by 4-6 weeks of age
|
growth/size/body
muscle
skeleton
|
N |
• no bone fractures or other skeletal abnormalities are seen
|
cellular
|
N |
• normal nuclear envelope morphology in MEFs
|
growth/size/body
|
N |
• improved growth compared to mice homozygous for Zmpste24tm1Sgy only
|
muscle
|
N |
• muscle strength is similar to wild-type
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm2Lgf mutation
(0 available);
any
Lmna mutation
(82 available)
Zmpste24tm1Sgy mutation
(2 available);
any
Zmpste24 mutation
(32 available)
|
|
|
skeleton
|
N |
• no bone fractures or other skeletal abnormalities are seen
|
cellular
|
N |
• far fewer misshapen nuclei in MEFs
|
growth/size/body
muscle
|
N |
• muscle strength is similar to wild-type
|
Analysis Tools