Phenotypes Associated with This Genotype

Genotype
MGI:3817506

• Allelic Composition: Lmna^tm1Lgf/Lmna⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

Lmna^tm1Lgf/Lmna⁺ mice exhibt kyphosis, rib fractures, and skull abnormalities

mortality/aging

premature death ( J:113119 , J:141165 , J:146099 )

• 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

abnormal cranial suture morphology ( J:113119 )

• cranial sutures have a zigzag appearance

abnormal zygomatic arch morphology ( J:113119 )

• by week 18, mice develop osteolytic lesions in the posterior portion of the zygomatic arch

micrognathia ( J:113119 )

abnormal rib morphology ( J:113119 , J:141165 )

• mice develop osteolytic lesions in the ribs (J:113119)

• ribs exhibit decreased bone density and cortical thickness compared to wild-type mice (J:141165)

rib fractures ( J:113119 , 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)

kyphosis ( J:113119 , J:141165 )

• mice develop kyphosis (J:113119)

• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype (J:113119)

abnormal bone structure ( J:113119 )

• mice exhibit osteolytic lesions on the ribs, zygomatic arch, clavicle, scapula, calvarium and mandible

decreased bone mineral density ( J:141165 )

• ribs exhibit decreased bone density compared to wild-type mice

abnormal bone mineralization ( J:113119 )

• mice exhibit poor bone mineralization

• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype

adipose tissue

decreased subcutaneous adipose tissue amount ( J:113119 )

• mice exhibit reduced subcutaneous adipose tissue compared to wild-type mice

• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype

decreased abdominal adipose tissue amount ( J:113119 )

• mice exhibit decreased abdominal adipose tissue compared to wild-type mice

• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype

decreased percent body fat/body weight ( J:141165 )

cellular

abnormal cell nucleus morphology ( J:100220 , J:141165 , J:146099 )

• 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/body

decreased body weight ( J:141165 , J:146099 )

weight loss ( J:113119 )

• mice begin to lose weight at 6 to 8 weeks of age

• however, treatment with FTI (a farnesyltransferase inhibitor) improves phenotype

behavior/neurological

behavior/neurological phenotype ( J:113119 )

N • unlike Zmpste24 knockout mice, grip strength is normal

craniofacial

abnormal cranial suture morphology ( J:113119 )

• cranial sutures have a zigzag appearance

abnormal zygomatic arch morphology ( J:113119 )

• by week 18, mice develop osteolytic lesions in the posterior portion of the zygomatic arch

micrognathia ( J:113119 )

integument

decreased subcutaneous adipose tissue amount ( J:113119 )

• 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		DO ID	OMIM ID(s)	Ref(s)
progeria		DOID:3911	OMIM:176670	J:113119