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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Lmnatm1.1Otin
targeted mutation 1.1, Carlos Lopez-Otin
MGI:5295747
Summary 6 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Lmnatm1.1Otin/Lmnatm1.1Otin involves: 129P2/OlaHsd * C57BL/6 MGI:5295749
hm2
Lmnatm1.1Otin/Lmnatm1.1Otin involves: 129P2/OlaHsd * C57BL/6NTac MGI:7311570
ht3
Lmnatm1.1Otin/Lmna+ involves: 129P2/OlaHsd * C57BL/6 MGI:5295754
ht4
Lmnatm1.1Otin/Lmna+ involves: 129P2/OlaHsd * C57BL/6NTac MGI:7311569
cx5
Lmnatm1.1Otin/Lmnatm1.1Otin
Nat10tm1a(KOMP)Wtsi/Nat10+
involves: 129P2/OlaHsd * C57BL/6NTac MGI:7311572
cx6
Lmnatm1.1Otin/Lmna+
Nat10tm1a(KOMP)Wtsi/Nat10+
involves: 129P2/OlaHsd * C57BL/6NTac MGI:7311574


Genotype
MGI:5295749
hm1
Allelic
Composition
Lmnatm1.1Otin/Lmnatm1.1Otin
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm1.1Otin mutation (0 available); any Lmna mutation (84 available)
phenotype observed in females
phenotype observed in males
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
• treatment with intraperitoneal injections of pyrophosphate over 9 weeks inhibits aortic calcification
• 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
• 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)
• MEFs have more misshapen nuclei with nuclear blebs than wild-type MEFs (J:177575)
• 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
• smaller lower incisors
• mutants develop cervicothoracic lordokyphosis
• 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
DO ID OMIM ID(s) Ref(s)
progeria DOID:3911 OMIM:176670
J:177575 , J:177632 , J:211388




Genotype
MGI:7311570
hm2
Allelic
Composition
Lmnatm1.1Otin/Lmnatm1.1Otin
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6NTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm1.1Otin mutation (0 available); any Lmna mutation (84 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

reproductive system
• due to reduced reproductive fitness
• however, normal oocyte production and fertilization with wild-type sperm

adipose tissue
• treatment with Remodelin partially rescues phenotype

cardiovascular system
• increased thickness that is partially rescued by Remodelin treatment

growth/size/body

immune system

renal/urinary system

skeleton

vision/eye

cellular

integument
• treatment with Remodelin partially rescues phenotype

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
progeria DOID:3911 OMIM:176670
J:261974




Genotype
MGI:5295754
ht3
Allelic
Composition
Lmnatm1.1Otin/Lmna+
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm1.1Otin mutation (0 available); any Lmna mutation (84 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mutants exhibit an average lifespan of 242 days (J:177632)

growth/size/body
• mutants start to lose weight at around 8 months of age

homeostasis/metabolism
• 8-fold decrease in plasma ATP concentrations
• 9-fold decrease in plasma pyrophosphate concentrations
• however, no differences in plasma phosphorus or calcium levels are seen
• at 8 months of age, heterozygotes show a decrease in serum glucose concentrations
• 29.5% higher levels of plasma alkaline phosphatase activity than controls

cellular
• mutants show nuclear abnormalities due to progerin accumulation (J:177632)
• MEFs have more misshapen nuclei with nuclear blebs than wild-type MEFs (J:177575)

cardiovascular system
• medial calcification in aortic arch and thoracic aorta at 30-34 weeks of age
• primary cultures of vascular smooth muscle cells from aortic tissue show a lower capacity to inhibit calcium deposition than control cells when incubated in calcifying medium
• aortic vascular smooth cells exhibit impaired capacity to synthesize extracellular pyrophosphate, show lower levels of extracellular ATP and intracellular ATP indicating impaired ATP synthesis, and have a lower COX:CS ratio indicating impaired mitochondrial function

muscle
• primary cultures of vascular smooth muscle cells from aortic tissue show a lower capacity to inhibit calcium deposition than control cells when incubated in calcifying medium
• aortic vascular smooth cells exhibit impaired capacity to synthesize extracellular pyrophosphate, show lower levels of extracellular ATP and intracellular ATP indicating impaired ATP synthesis, and have a lower COX:CS ratio indicating impaired mitochondrial function

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
progeria DOID:3911 OMIM:176670
J:211388




Genotype
MGI:7311569
ht4
Allelic
Composition
Lmnatm1.1Otin/Lmna+
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6NTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm1.1Otin mutation (0 available); any Lmna mutation (84 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• premature aging as in homozygotes with delayed onset

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
progeria DOID:3911 OMIM:176670
J:261974




Genotype
MGI:7311572
cx5
Allelic
Composition
Lmnatm1.1Otin/Lmnatm1.1Otin
Nat10tm1a(KOMP)Wtsi/Nat10+
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6NTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm1.1Otin mutation (0 available); any Lmna mutation (84 available)
Nat10tm1a(KOMP)Wtsi mutation (2 available); any Nat10 mutation (72 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• delayed compared to mice homozygous for the Lmnatm1.1Otin and wild-type Nat10

reproductive system
N
• unlike mice homozygous for the Lmnatm1.1Otin, mice do not exhibit penis prolapse
• partially rescued compared to mice homozygous for the Lmnatm1.1Otin and wild-type Nat10

skeleton
• delayed compared to mice homozygous for the Lmnatm1.1Otin and wild-type Nat10

vision/eye
N
• unlike mice homozygous for the Lmnatm1.1Otin, mice do not exhibit keratoconjunctivitis sicca

cardiovascular system
• delayed onset

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
progeria DOID:3911 OMIM:176670
J:261974




Genotype
MGI:7311574
cx6
Allelic
Composition
Lmnatm1.1Otin/Lmna+
Nat10tm1a(KOMP)Wtsi/Nat10+
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6NTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lmnatm1.1Otin mutation (0 available); any Lmna mutation (84 available)
Nat10tm1a(KOMP)Wtsi mutation (2 available); any Nat10 mutation (72 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• significantly delayed compared to in Lmnatm1.1Otin homozygotes

skeleton
• significantly delayed compared to in Lmnatm1.1Otin homozygotes

growth/size/body
• significantly delayed compared to in Lmnatm1.1Otin homozygotes

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
progeria DOID:3911 OMIM:176670
J:261974





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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
11/19/2024
MGI 6.24
The Jackson Laboratory