All Phenotypes Lmna<tm2.1Gbon> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lmna^tm2.1Gbon/Lmna^tm2.1Gbon	involves: 129 * C57BL/6	MGI:5306920
ht2	Lmna^tm2.1Gbon/Lmna⁺	involves: 129 * C57BL/6	MGI:5906504

Allelic Composition	Lmna^tm2.1Gbon/Lmna^tm2.1Gbon
Genetic Background	involves: 129 * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmna^tm2.1Gbon mutation (0 available); any Lmna mutation (82 available)

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

mortality/aging

postnatal lethality, complete penetrance ( J:180603 )

• start to die by P15 and all are dead by P19

growth/size/body

weight loss ( J:180603 )

• start to lose weight by P12

postnatal growth retardation ( J:180603 )

• apparent by P5

slow postnatal weight gain ( J:180603 )

• by P12 mice are about 50% lighter compared to littermate controls

muscle

abnormal myocardial fiber morphology ( J:180603 )

• lipid droplets remain high in cardiomyocytes at P14 unlike in controls where droplets disappear by P5

abnormal muscle development ( J:180603 )

• defect in maturation

decreased skeletal muscle fiber size ( J:180603 )

• decrease in cross-sectional area at P14 in the gastrocnemius muscle

centrally nucleated skeletal muscle fibers ( J:180603 )

• significant increase in the number of central nuclei at P5, P8 and P14

• however, no signs of inflammation, necrosis, or fibrosis are seen

cardiovascular system

abnormal myocardial fiber morphology ( J:180603 )

• lipid droplets remain high in cardiomyocytes at P14 unlike in controls where droplets disappear by P5

abnormal heart development ( J:180603 )

• expression analysis indicates a defect in cardiac maturation

decreased heart weight ( J:180603 )

• heart weight to tibia length ratio is markedly lower at P14 but not at P0

behavior/neurological

abnormal behavior ( J:180603 )

• slight delay in walk acquisition compared to littermates

abnormal gait ( J:180603 )

• waddling gait with an increased number of falls apparently due to hindquarter blockade

adipose tissue

decreased white adipose tissue amount ( J:180603 )

• marked reduction or absence of white adipose tissue

cellular

abnormal cell differentiation ( J:180603 )

• by 10 days after induction of adipogenic differentiation MEFs fail to accumulate lipid droplets unlike wild-type MEFs

homeostasis/metabolism

hypoglycemia ( J:180603 )

• develop progressive hypoglycemia starting at P12

• by P14 blood glucose levels are only about 45% of the level in control littermates

decreased circulating insulin level ( J:180603 )

abnormal urine homeostasis ( J:180603 )

• C2- and C6-acylcarnitine levels are higher

renal/urinary system

abnormal urine homeostasis ( J:180603 )

• C2- and C6-acylcarnitine levels are higher

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital muscular dystrophy due to LMNA mutation		DOID:0110640	OMIM:613205	J:180603

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

mortality/aging

premature death ( J:198526 )

• mice die between 35 and 70 weeks of age

• death occurs about 15-20 weeks after reduced fractional shortening

cardiovascular system

cardiac muscle degeneration ( J:198526 )

• at end stage, degenerative changes are seen in cardiac tissues with disrupted sarcomeres, myofibrillar lysis, vesicular proliferation of sarcomeric reticulum, intracytoplasmic junctions, electron dense residual bodies, and pericellular fibrosis

abnormal heart morphology ( J:198526 )

• large proportion of nuclei in the heart are more elongated and thinner at 10, 30, and 57 weeks of age and these nuclei have enlarged nuclear intermembrane space in young asymptomatic mice

• mice with mild cardiac dysfunction show severe alterations in cardiac nuclei, such as extremely enlarged nuclear intermembrane space, accumulation of large perinuclear vacuoles, or envelope rupture with extravasations of chromatin into the cytoplasm

increased heart atrium size ( J:198526 )

• atrial enlargement

cardiac hypertrophy ( J:198526 )

dilated heart left ventricle ( J:198526 )

• increase in left ventricular end-diastolic diameter

• however, no major wall thinning is seen

cardiac fibrosis ( J:198526 )

• at end stage, the left ventricle shows slight fibrosis

dilated cardiomyopathy ( J:198526 )

• mice exhibit decreased fractional shortening and increased left ventricle end-diastolic diameter indicating dilated cardiomyopathy

decreased cardiac muscle contractility ( J:198526 )

• progressive development of cardiac dysfunction from 32 to 70 weeks of age

• decrease in fractional shortening which starts a bit earlier in males than in females

abnormal heart echocardiography feature ( J:198526 )

• echocardiography indicates decreased fractional shortening and increased left ventricle end-diastolic diameter without wall thinning

decreased heart rate ( J:198526 )

• slight bradycardia is seen at the very end stages of the dilated cardiomyopathy

prolonged PR interval ( J:198526 )

• higher PR interval is seen at the very end stages of the dilated cardiomyopathy

prolonged QRS complex duration ( J:198526 )

• QRS complex broadening is seen at the very end stages of the dilated cardiomyopathy

congestive heart failure ( J:198526 )

• mice eventually present with congestive heart failure demonstrated by left ventricle hypokinesia and lung edema

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:198526 )

N	• 57 week old mice do not exhibit metabolic defects

pulmonary edema ( J:198526 )

• lung edema in mice with congestive heart failure