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Phenotypes Associated with This Genotype
Genotype
MGI:4459466
Allelic
Composition
LmnaDhe/Lmna+
Genetic
Background
B6(D2)-LmnaDhe/TyGrsrJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
LmnaDhe mutation (1 available); any Lmna mutation (67 available)
phenotype observed in females
phenotype observed in males
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

hematopoietic system
• nuclear lamina meshwork of peritoneal macrophages appears rugous, disintegrative, or even collapsed and nuclear volumes are large
• however, mice exhibit normal macrophage migration elicited by thioglycollate

immune system
• 100% penetrance of otitis media as early as P12
• cells of acute inflammatory response begin to perfuse the middle ear cavity, to infiltrate the mesenchymal cells and to block the Eustachian tube at P12
• at 8 weeks of age, cells of chronic inflammatory response pervade the entire middle ear cavity
• acute inflammatory cells and plasma fluids infiltrate the middle ear cavity extensively at P30
• from 2-8 months, various chronic suppurative middle ear inflammation occurs, with or without cholesteatoma
• macrophage activation is observed
• nuclear lamina meshwork of peritoneal macrophages appears rugous, disintegrative, or even collapsed and nuclear volumes are large
• however, mice exhibit normal macrophage migration elicited by thioglycollate

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
• 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
• suture tissue is hypoplastic, forming a much looser, thinner connection of the plates
• shorter, wider skull
• in keeping with the reduction in body size
• bone growth deficiency
• maxillary incisor and the diastema (the maxillary arch) are both abnormally short in the mutant
• underdeveloped lower jaw, inferior brachygnathism
• superior brachygnathism
• decreased nose length
• short pinnae

hearing/vestibular/ear
• ear hyperemia
• short pinnae
• bullae are smaller
• middle ear is undeveloped at P6
• the tympanic membrane is undeveloped at P12
• middle ear is undeveloped at P6
• middle ear cholesteatoma is seen in some ears
• typical cholesterol crystals are encysted by the hyperproliferative mucous epithelium and necrotic keratinizing squamous epithelial debris
• local suppurative abscess form in some middle ear cavities
• proliferative goblet cells in the middle ear
• by 10 weeks of age, the cilia of the middle ear pseudostratified ciliated columnar epithelium exhibits severe pathology indicative of otitis media progression
• abnormal positioning of the Eustachian tube with a greater mean intersection angle
• the mean length of the bony part of the Eustachian tube is smaller and width is greater than in wild-type resulting in a dilated anamorphic Eustachian tube
• at P12, with middle ear cavitation still progressing, dysplasia with dilation of the Eustachian tube is seen
• at 8 weeks of age, the Eustachian tube is distorted with dilation and exhibits poorly aligned and shorted or obsolescent cilia
• tympanic membrane adherence
• the tympanic membrane is undeveloped at P12
• tympanic membrane shows a shortened subuliform light cone
• at 8 weeks of age, the tympanic membrane is thickened and retracts into the middle ear cavity
• tympanometry shows that tympanometric values of volume are lower at 3 weeks of age but not other ages, values of compliance are lower at all time points from 3 weeks to 8 months of age, pressure of the middle ear is more negative, mean gradient values are higher at 1 month of age and 5 month old mice show an abnormal C type curve instead of the normal A type curve in scanning tympanograms
• ABR threshold from P16 to 4 months of age are elevated
• at 3 months of age, mice have distortion product otoacoustin emission (DPOAE) 10-43.5 dB lower than those of wild-type mice
• hearing impairment begins at lower stimulus frequencies (click and 8 kHz) and higher stimulus frequencies become affected with age
• 100% penetrance of otitis media as early as P12
• cells of acute inflammatory response begin to perfuse the middle ear cavity, to infiltrate the mesenchymal cells and to block the Eustachian tube at P12
• at 8 weeks of age, cells of chronic inflammatory response pervade the entire middle ear cavity
• acute inflammatory cells and plasma fluids infiltrate the middle ear cavity extensively at P30
• from 2-8 months, various chronic suppurative middle ear inflammation occurs, with or without cholesteatoma
• macrophage activation is observed

respiratory system
• roof of the nasopharynx is abnormal as there is barely a gap between the tissue of the nasopharynx and the palate and the roof the nasopharynx is nearly fused to the palate bone

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
• 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
• suture tissue is hypoplastic, forming a much looser, thinner connection of the plates
• shorter, wider skull
• in keeping with the reduction in body size
• bone growth deficiency
• maxillary incisor and the diastema (the maxillary arch) are both abnormally short in the mutant
• 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)
• nuclear lamina meshwork of peritoneal macrophages appears rugous, disintegrative, or even collapsed (J:188496)
• 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
• females exhibit a lower calcium/phosphorus ratio due to an increase of phosphorus rather than a decrease in calcium

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
otitis media DOID:10754 OMIM:166760
J:188496
progeria DOID:3911 OMIM:176670
J:171665


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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
06/12/2018
MGI 6.12
The Jackson Laboratory