Mouse Genome Informatics
ht
    Lmnatm1Lgf/Lmna+
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Lmnatm1Lgf/Lmna+ mice exhibt kyphosis, rib fractures, and skull abnormalities

mortality/aging
• 50% of mice become malnourished and are euthanized by week 27 (J:113119)
• all mice die by 40 week of age (J:113119)
• mice die by 35 weeks of age (J:141165)
• mice die at 30 weeks (J:146099)

skeleton
• cranial sutures have a zigzag appearance
• by week 18, mice develop osteolytic lesions in the posterior portion of the zygomatic arch
• mice develop osteolytic lesions in the ribs (J:113119)
• ribs exhibit decreased bone density and cortical thickness compared to wild-type mice (J:141165)
• mice are pre-disposed to rib fractures near the costovertebral junction unlike wild-type mice (J:113119)
• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype (J:113119)
• mice develop progressive rib fractures near the costovertebral joints as they age (J:141165)
• mice develop kyphosis (J:113119)
• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype (J:113119)
• mice exhibit osteolytic lesions on the ribs, zygomatic arch, clavicle, scapula, calvarium and mandible
• ribs exhibit decreased bone density compared to wild-type mice
• mice exhibit poor bone mineralization
• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype

adipose tissue
• mice exhibit decreased abdominal adipose tissue compared to wild-type mice
• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype
• mice exhibit reduced subcutaneous adipose tissue compared to wild-type mice
• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype

cellular
• primary fibroblast lines that are heterozygous display increased nuclear blebbing, which is diminished by treatment with farnesyltransferase blocker PB-43 (J:100220)
• mouse embryonic fibroblasts exhibit misshapen nuclei (J:141165)
• mouse embryonic fibroblasts exhibit misshapen nuclei unlike wild-type cells (J:146099)

growth/size
• mice begin to lose weight at 6 to 8 weeks of age
• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype

behavior/neurological
N
• unlike Zmpste24 knockout mice, grip strength is normal (J:113119)

craniofacial
• cranial sutures have a zigzag appearance
• by week 18, mice develop osteolytic lesions in the posterior portion of the zygomatic arch

integument
• mice exhibit reduced subcutaneous adipose tissue compared to wild-type mice
• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype

Mouse Models of Human Disease
OMIM IDRef(s)
Hutchinson-Gilford Progeria Syndrome; HGPS 176670 J:113119