Mouse Genome Informatics
hm
    Lmnatm2Stw/Lmnatm2Stw
involves: 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• mice die between 4 and 5 weeks of age
• most obvious signs of premature aging are thickening of the epidermal layer by hyperkeratosis, thinning of the underlying dermis, atrophy of the accompanying muscle, and absence of the subcutaneous fat layer

behavior/neurological
• slight waddling gait

cardiovascular system
• subtle anomalies consistent with pulmonary hypertension
• a decrease in the number of myocytes with a compensatory increase in the fibrocyte numbers such that the total number of cells in the heart is the same as in wild-type

craniofacial
• about half of mutants have a gap between the lower two incisors, which are yellowed

endocrine/exocrine glands
• reduction in numbers of sebaceous glands
• reduction in the numbers of eccrine glands

growth/size
• within 4-6 days after birth, mice develop severe growth retardation

hearing/vestibular/ear

limbs/digits/tail
N
• no osteolysis of terminal digits (J:83382)

muscle
• a decrease in the number of myocytes with a compensatory increase in the fibrocyte numbers such that the total number of cells in the heart is the same as in wild-type
• mild to moderate degeneration mixed with hypoplasia and/or atrophy
• mild to moderate degeneration of skeletal muscles, including pharyngeal, paravertebral, shoulder, hip, tibia, radius, femur, humerus, and tongue
• occurs by 4 weeks of age, indicating premature aging in mutants

reproductive system

skeleton
• in 50% of mutants, at least one scapula is smaller, thinner, and misshapen compared with controls
• decrease in total bone mineral density of 25-30% compared to controls
• 4 week old mutants show a decrease in number and size of trabeculae
• 4 week old mutants exhibit a decrease in the cortex width of vertebrae and femur, indicating osteoporosis

adipose tissue
• at 4 weeks of age, an indictor of premature aging

digestive/alimentary system
• hypoplasia and/or atrophy of esophageal muscles suggesting either incomplete development or loss of muscle mass

cellular
• nuclear morphology is disrupted in mouse embryo fibroblasts; 58% of mutant cells have discontinuities of the nuclear envelope compared to 20% of heterozygotes and 5.6% of wild-type cells

integument
• at 4 weeks of age, an indictor of premature aging
• reduction in numbers of sebaceous glands
• reduction in the numbers of eccrine glands
• decrease in follicle density
• increase in collagen deposition in the skin
• thinning of the dermal layer is seen at 4 weeks of age
• seen at 4 weeks of age, indicating premature aging

Mouse Models of Human Disease
OMIM IDRef(s)
Hutchinson-Gilford Progeria Syndrome; HGPS 176670 J:83382