Phenotypes Associated with This Genotype

Genotype
MGI:5306920

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

• ♀: 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