Mouse Genome Informatics
hm
    Lmnatm1.1Otin/Lmnatm1.1Otin
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• mutants exhibit an average lifespan of 103 days (J:177632)
• mutants exhibit premature aging as indicated by an increase in senescence-associated beta-galactosidase staining in the liver and kidney at 3 months of age

growth/size/body
• smaller lower incisors
• mutants exhibit progressive weight loss after 3 weeks of age
• mutants show reduced growth rates after 3 weeks of age, with progressive weight loss

reproductive system

cardiovascular system
• seen in 10 week old mice (J:211388)
• treatment with intraperitoneal injections of pyrophosphate over 9 weeks inhibits aortic calcification (J:211388)
• mutants exhibit loss of vascular smooth muscle cells in the aortic arch, but not in the medial layer of the thoracic aorta
• blood pressure appears normal but mutants progressively develop bradycardia between 9 and 15 weeks of age
• ECG indicates prolonged QRS waves without changes in the PR interval, indicating altered heart ventricular depolarization
• however, no differences in systolic function or diastolic function are seen

cellular
• MEFs have more misshapen nuclei with nuclear blebs than wild-type MEFs (J:177575)
• mutants show nuclear abnormalities due to progerin accumulation (J:177632)
• 81% of cultured fibroblasts at passage 5 contain large and abnormally shaped nuclei (J:177632)
• 81% of cultured fibroblasts at passage 5 contain large and abnormally shaped nuclei with foci highly stained with anti-gammaH2AX antibodies, indicating genotoxic stress

craniofacial
• skulls are reduced in size
• smaller lower incisors

adipose tissue
• older mutants exhibit a generalized loss of principal fat deposits, with a loss of the subcutaneous fat layer

homeostasis/metabolism
• mutants show a decrease in serum levels of insulin-like factor 1
• at 2 months of age, mutants show a decrease in serum glucose concentrations that leads to extreme hypoglycemia by 3 months of age

immune system
• thymus exhibits a marked involution relative to wild-type mice, even after accounting for body size differences
• spleen exhibits a marked involution relative to wild-type mice, even after accounting for body size differences

integument
• older mutants exhibit a generalized loss of principal fat deposits, with a loss of the subcutaneous fat layer
• older mutants exhibit attrition of hair follicles

behavior/neurological

muscle
• mutants exhibit loss of vascular smooth muscle cells in the aortic arch, but not in the medial layer of the thoracic aorta

hematopoietic system
• thymus exhibits a marked involution relative to wild-type mice, even after accounting for body size differences
• spleen exhibits a marked involution relative to wild-type mice, even after accounting for body size differences

skeleton
• skulls are reduced in size
• mutants develop cerviocothoracic lordokyphosis (abnormal posture and curvature of the spine)
• tibias exhibit increased porosity
• tibias exhibit reduced bone density
• bone volume of tibias is decreased
• tibias exhibit reduced cortical thickness

endocrine/exocrine glands
• thymus exhibits a marked involution relative to wild-type mice, even after accounting for body size differences

Mouse Models of Human Disease
OMIM IDRef(s)
Hutchinson-Gilford Progeria Syndrome; HGPS 176670 J:177575 , J:177632 , J:211388