Mouse Genome Informatics
ht
    LmnaDhe/Lmna+
B6(D2)-LmnaDhe/TyGrsrJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

LmnaDhe/Lmna+ mice (right) have a sparse and gray coat, small size and small pinnae

mortality/aging
• coat turns gray around 12 weeks of age
• however, lifespan is similar to controls

craniofacial
• patent sutures, in all cranial vault and facial sutures including the premaxillary/maxillary sutures
• at six weeks the parietal and interparietal bones do not overlap and the suture tissue is hypoplastic, forming a much looser, thinner connection of the plates
• suture tissue is hypoplastic, forming a much looser, thinner connection of the plates
• suture tissue is hypoplastic, forming a much looser, thinner connection of the
• at 1 week of age, there is a gap between the the edges of the parietal bones and these bones are connected by a much thinner band of connective tissue
• shorter, wider skull
• in keeping with the reduction in body size
• bone growth deficiency
• underdeveloped lower jaw, inferior brachygnathism
• superior brachygnathism
• maxillary incisor and the diastema (the maxillary arch) are both abnormally short in the mutant
• decreased nose length
• short pinnae

hearing/vestibular/ear
• short pinnae

skeleton
• patent sutures, in all cranial vault and facial sutures including the premaxillary/maxillary sutures
• at six weeks the parietal and interparietal bones do not overlap and the suture tissue is hypoplastic, forming a much looser, thinner connection of the plates
• suture tissue is hypoplastic, forming a much looser, thinner connection of the plates
• suture tissue is hypoplastic, forming a much looser, thinner connection of the
• at 1 week of age, there is a gap between the the edges of the parietal bones and these bones are connected by a much thinner band of connective tissue
• shorter, wider skull
• in keeping with the reduction in body size
• bone growth deficiency
• underdeveloped lower jaw, inferior brachygnathism
• superior brachygnathism
• low bone mineral density of skull and whole body
• skull mineralization defects

adipose tissue

pigmentation
• turns gray around 12 weeks of age

cellular
• nuclei appear larger and nuclear volume is greater than in wild-type mice
• fibroblasts exhibit extensive aneuploidy, with a higher fraction of cells greater than 4C and chromosome numbers ranging from 38 to 104 chromosomes per nucleus
• grossly abnormal nuclear lamina of cultured primary calvarial osteoblasts with various numbers of nuclear lamina blebs, discreet balloon-like outpocketings of the nuclear envelope (J:160175)
• skin fibroblasts exhibit aberrant nuclear lamina morphology, with nuclear membranes showing large blebs and lobulations (J:171665)
• patches of irregularity in the normal criss-cross pattern of LMNA and LMNB meshworks are seen (J:171665)
• increase in DNA damage in interphase
• mutant cell cultures have an increased proportion of cells in anaphase compared to normal cells
• mitotic defects such as aneuploidy, lagging chromosomes, and anaphase bridges associated with low levels of activated RB1 and CAPD3
• LMNA expression and assembly at the nuclear lamina is perturbed during interphase and mitosis
• fibroblasts exhibit mitotic chromosome cohesion defects
• defects in mitotic spindle checkpoint
• fibroblasts grow significantly slower that wild-type fibroblasts

growth/size/body
• maxillary incisor and the diastema (the maxillary arch) are both abnormally short in the mutant
• decreased nose length
• short pinnae

reproductive system

vision/eye

integument
• turns gray around 12 weeks of age
• scruffy coat

homeostasis/metabolism
• increase in DNA damage in interphase

Mouse Models of Human Disease
OMIM IDRef(s)
Hutchinson-Gilford Progeria Syndrome; HGPS 176670 J:171665