Mouse Genome Informatics
hm1
    Lmnatm1Stw/Lmnatm1Stw
involves: 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all die by 8 weeks of age

cellular
• in MEFs, nuclei appear elongated or irregular with loss of B-type lamins from 1 pole, slight clustering of nuclear pore complexes, and loss of emerin from the nuclear envelope into the cytoplasm
• in MEFs and hepatocytes, patchy thinning or loss of heterochromatin from the nuclear face of the inner nuclear membrane is seen and these regions also lack identifiable nuclear pore complexes
• the nuclear envelope is more easily fragmented during isolation

growth/size/body
• at 4 weeks, mean body weight is about 50% of wild-type and heterozygous littermates
• growth retardation is seen by 2-3 weeks of age and growth ceases by 4 weeks of age

muscle
• muscles surrounding the femur and perivertebral muscles are dystrophic while cardiac muscle is variably affected with ventricular muscle more severely impaired; however, muscles in the head, tongue and diaphragm are relatively normal
• muscle fibers are variably affected with those closer to the bone being more severely impaired
• no elevation of serum creatine kinase levels are detected
• in the heart, some ventricular myocytes show signs of degeneration often associated with patchy mineralization

behavior/neurological
• at 3-4 weeks mice have reduced grip strength
• at 3-4 weeks mice display a stiff walking posture with splayed hind legs

skeleton
• progressive kyphoscoliosis starting around 3-4 weeks of age

adipose tissue
• absence of white fat

nervous system
• sciatic nerve axon density is reduced, axon diameter is increased, and nonmyelinated axons are present
• sciatic nerve axon density is reduced, axon diameter is increased, and nonmyelinated axons are presen
• nonmyelinated axons are present in the sciatic nerve

immune system
• probably secondary to physiological stress
• probably secondary to physiological stress

hematopoietic system
• probably secondary to physiological stress
• probably secondary to physiological stress

endocrine/exocrine glands
• probably secondary to physiological stress


Mouse Genome Informatics
hm2
    Lmnatm1Stw/Lmnatm1Stw
involves: 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die by 4-6 weeks of age

growth/size/body

muscle

reproductive system
(J:88595)
• spermatids and spermatozoa are largely absent (J:88595)
• increased frequency of leptotene and zygotene spermatocytes and decreased frequency of pachytene and diplotene spermatocytes resulting from arrest and apoptosis of spermatocytes during the pachytene stage (J:88595)
• however, oogenesis in females is normal (J:88595)
• unpaired chromosomes and/or improperly paired sex chromosomes and failure to progress through prophase I are seen (J:88595)

endocrine/exocrine glands
(J:88595)


Mouse Genome Informatics
hm3
    Lmnatm1Stw/Lmnatm1Stw
involves: 129S1/Sv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• at 4 weeks serum glucose levels are decreased however insulin levels are only slightly and not significantly decreased
• only significant in 4 week old females although levels in males also tend to be lower

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Lipodystrophy, Familial Partial, Type 2; FPLD2 151660 J:75101


Mouse Genome Informatics
ht4
    Lmnatm1Stw/Lmna+
involves: 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• in many MEFs, nuclei appear elongated but distribution of nuclear envelope proteins is normal except for increased levels of cytoplasmic emerin


Mouse Genome Informatics
ht5
    Lmnatm1Stw/Lmna+
involves: 129S1/Sv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• on a high fat diet, females develop mild insulin resistance that correlates with increased body weight, no insulin resistance is seen in males
• on a normal diet, serum glucose, insulin, and triglyceride levels are normal, insulin sensitivity and glucose tolerance
• on a high fat diet, females develop increased insulin but not glucose levels

adipose tissue
N
• no signs of lipoatrophy are seen (J:75101)

liver/biliary system
N
• liver morphology is normal (J:75101)

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Lipodystrophy, Familial Partial, Type 2; FPLD2 151660 J:75101


Mouse Genome Informatics
ht6
    Lmnatm1Lgf/Lmnatm1Stw
involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die between 10 and 14 weeks of age

skeleton
• mice develop fractures in the extremities by 8 weeks of age


Mouse Genome Informatics
ht7
    Lmnatm1Stw/Lmnatm7Lgf
involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular


Mouse Genome Informatics
ht8
    Lmnatm1Stw/Lmnatm2Lgf
involves: 129S1/Sv * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• viable and fertile with normal growth and muscle strength


Mouse Genome Informatics
cx9
    Lmnatm1Stw/Lmna+
Zmpste24tm1Sgy/Zmpste24tm1Sgy

involves: 129S1/Sv * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
N
• no bone fractures or other skeletal abnormalities are seen (J:95274)

cellular
N
• normal nuclear envelope morphology in MEFs (J:95274)

growth/size/body
N
• improved growth compared to mice homozygous for Zmpste24tm1Sgy only (J:95274)

muscle
N
• muscle strength is similar to wild-type (J:95274)


Mouse Genome Informatics
cx10
    Lmnatm1Stw/Lmnatm1Stw
Zmpste24tm1Sgy/Zmpste24+

involves: 129S1/Sv * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die by 4-6 weeks of age

growth/size/body

muscle


Mouse Genome Informatics
cx11
    Lmnatm1Stw/Lmnatm1Stw
Zmpste24tm1Sgy/Zmpste24tm1Sgy

involves: 129S1/Sv * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die by 4-6 weeks of age

growth/size/body

muscle