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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Terctm1Rdp
targeted mutation 1, Ronald DePinho
MGI:1857930
Summary 17 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Terctm1Rdp/Terctm1Rdp B6J.Cg-Terctm1Rdp MGI:5695524
hm2
Terctm1Rdp/Terctm1Rdp involves: 129/Sv * C57BL/6 * C57BL/6J * SJL MGI:4820640
hm3
Terctm1Rdp/Terctm1Rdp involves: 129/Sv * C57BL/6J * SJL MGI:2174766
hm4
Terctm1Rdp/Terctm1Rdp involves: FVB/N MGI:4365574
cx5
Dmdmdx-4Cv/Dmdmdx-4Cv
Terctm1Rdp/Terctm1Rdp
B6.Cg-Terctm1Rdp Dmdmdx-4Cv MGI:5529018
cx6
Terctm1Rdp/Terctm1Rdp
Tinf2tm2.2Tdl/Tinf2+
involves: 129 * BALB/cJ * C57BL/6 * SJL MGI:5556401
cx7
Terctm1Rdp/Terctm1Rdp
Terf1tm1Tdl/Terf1tm1Tdl
involves: 129S2/SvPas MGI:2677844
cx8
Pms2tm1Lisk/Pms2tm1Lisk
Terctm1Rdp/Terctm1Rdp
involves: 129/Sv * 129S2/SvPas * C57BL/6 * C57BL/6J * SJL MGI:4820641
cx9
Pot1btm1.1Schg/Pot1btm1.1Schg
Terctm1Rdp/Terctm1Rdp
involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL MGI:3831883
cx10
Pot1btm1.1Schg/Pot1btm1.1Schg
Terctm1Rdp/Terc+
involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL MGI:3831884
cx11
Terctm1Rdp/Terctm1Rdp
Wrntm1Lgu/Wrntm1Lgu
involves: 129/Sv * BALB/c * C57BL/6 * SLJ MGI:3700822
cx12
Terctm1Rdp/Terctm1Rdp
Tg(KRT5-Tert)8043Blas/0
involves: 129/Sv * C57BL/6 * C57BL/6J * DBA/2 * SJL MGI:3700845
cx13
Terctm1Rdp/Terctm1Rdp
Tg(KRT5-Terf2)PMBlas/Y
involves: 129/Sv * C57BL/6 * CBA * SJL MGI:6258421
cx14
Dmdmdx/Y
Terctm1Rdp/Terc+
involves: 129/Sv * C57BL/6J * C57BL/10ScSn * SJL MGI:4936867
cx15
Dmdmdx/Y
Terctm1Rdp/Terctm1Rdp
involves: 129/Sv * C57BL/6J * C57BL/10ScSn * SJL MGI:4936865
cx16
Cdkn2atm1Rdp/Cdkn2atm1Rdp
Terctm1Rdp/Terctm1Rdp
involves: 129/Sv * C57BL/6J * SJL MGI:3719052
cx17
Cdkn2atm1Rdp/Cdkn2a+
Terctm1Rdp/Terctm1Rdp
involves: 129/Sv * C57BL/6J * SJL MGI:3719054


Genotype
MGI:5695524
hm1
Allelic
Composition
Terctm1Rdp/Terctm1Rdp
Genetic
Background
B6J.Cg-Terctm1Rdp
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• increase in bone marrow fat content in aged mice
• 41.7% and 84.9% decrease in femur bone volume at 3 months of age and in aged mice, respectively
• 27.1% and 49.3% increase in cortical porosity in young and aged mice, respectively
• 4% and 28.2% decrease in cortical bone area in young and aged mice, respectively
• decrease in cortical thickness in both young and aged mice
• young femurs show a more rod-like trabecular structure
• increase in trabecular separation
• accelerated bone aging characteristic features of human senile osteoporosis
• osteoid significantly decreases with age
• bone shows mechanical alterations including an increase in structure model index, a decrease in anisotropy and a decrease in the moment of inertia
• mineralized surface, mineral apposition rate, and bone formation rate dramatically decline with age

adipose tissue
• increase in bone marrow fat content in aged mice

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
osteoporosis DOID:11476 OMIM:166710
J:213181




Genotype
MGI:4820640
hm2
Allelic
Composition
Terctm1Rdp/Terctm1Rdp
Genetic
Background
involves: 129/Sv * C57BL/6 * C57BL/6J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• median survival is reduced in successive generations compared to in wild-type mice

digestive/alimentary system
• regardless of generation
• intestinal cell proliferation is impaired compared to in wild-type mice
• mice exhibit mild to severe intestinal atrophy unlike wild-type mice that worsens in successive generations

cellular
• telomeres become progressively shorter each generation unlike in wild-type mice
• mouse embryonic fibroblasts (MEFs) from third generation mice exhibit decreased immortalization ability under a 3T3 cell passage protocol compared with similarly treated wild-type cells
• sister chromatid exchange in MEFs is increased compared to in wild-type cells
• cells from the small intestine exhibit an increase in gamma-H2AX foci, indicative of DNA damage, compared with cells from wild-type mice
• regardless of generation
• intestinal cell proliferation is impaired compared to in wild-type mice
• mouse embryonic fibroblasts (MEFs) exhibit in increase in microsatellite instability compared with wild-type cells
• end-to-end chromosome fusions in MEFs are increased compared to in wild-type cells
• MEFs from late generation mice exhibit an increase in chromosome breaks, fragments, bivalent recombination figures, and complex aberrations compared with wild-type cells

neoplasm
• the incidence of lymphomas decreases in successive generation

homeostasis/metabolism
• cells from the small intestine exhibit an increase in gamma-H2AX foci, indicative of DNA damage, compared with cells from wild-type mice




Genotype
MGI:2174766
hm3
Allelic
Composition
Terctm1Rdp/Terctm1Rdp
Genetic
Background
involves: 129/Sv * C57BL/6J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Axial/lateral elements of synaptonemal complexes and apoptosis of seminiferous tubules in Terctm1Rdp/Terctm1Rdp mice

mortality/aging
• older (6-8 months) fifth generation mutants that show sudden loss in body weight and activity die 7-12 hours after the manifestation of these phenotypes
• a fraction of homozygous embryos from late generation homozygous matings do not survive gestation to completion or die immediately after birth (J:53600)
• only 74% of homozygous fetuses from late generation pregnant females are alive (J:89751)
• late generation mutants exhibit accelerated degeneration as indicated by hair graying, alopecia, kyphosis, reduced body size and weight, and fragility

cellular
• second and fifth generation mutants exhibit decreased cardiac myocyte proliferation
• lack of perinuclear distribution of telomeres in fourth generation mutants
• embryonic fibroblast cells derived from mutant mice after the fourth generation lacked detectable telomeric repeats and were often aneupolid with chromosomal abnormalities, including end to end fusions (J:43517)
• splenocytes from non-immunized fifth generation mutants contain shorter telomere lengths than wild-type (J:60223)
• upon immunization with an antigen, proliferating splenocyte telomeres are shortened during germinal center formation, unlike in wildtype mice which show elongation of telomeres, however telomeres are longer than seen in non-immunized mutants (J:60223)
• telomere shortening occurs in both meiocytes with normal and abnormal synapsis (J:89751)
• keratinocytes exhibit a significant decrease in average telomere length compared with wild-type cells (J:96945)
• cardiac myocytes of second and fifth generation mutants show telomere shortening, with cardiomyocytes from older mutants having shorter telomeres than in younger mutants (J:110900)
• the anaphase bridge index (ABI) is increased in late-generation (G4/G5) intestinal crypts indicating telomere dysfunction (J:120065)
• the number of oocytes that form synaptonemal complexes is decreased
• apoptosis is increased 5-fold in seminiferous tubules of G4 homozygotes; apoptosis is found in the outer layers of spermatocytes whereas the inner layer of spermatogonia remains intact
• in response to telomere shortening, male germ cells undergo apoptosis (J:89751)
• apoptotic depletion of germ cells in late generation mutants (J:120065)
• apoptosis of male germ cells and in the GI crypts of late generation mutants
• fifth generation mutants exhibit a 63% increase in cardiomyocyte apoptosis
• splenocytes from immunized fifth and sixth generation mice exhibit a small increase in apoptosis after mitogen treatment
• E10.5 embryos with neural tube defects exhibit an increase in apoptosis
• splenocytes (from both non-immunized and immunized) from sixth generation mutants show a decrease in the proliferative response to B and T cell mitogens
• splenocytes (from both non-immunized and immunized) from sixth generation mutants show a decrease in the proliferative response to B and T cell mitogens

neoplasm
• fifth generation mutants show decreased tumor growth rate and lower tumor formation efficiency upon dermal or subcutaneous melanoma cell injection
• tumors that are induced in fifth generation mutants show decreased replication potential and increased apoptotic rates
• first generation mutants are slightly less susceptible to DMBA + TPA induced skin tumorigenesis, with a delay in papilloma formation compared to wild-type and papillomas that do not progress to lesions bigger than 8 mm

cardiovascular system
• late generation mutants show decreased angiogenic potential in a basement membrane matrix assay
• microvessel density is decreased in the induced tumors of fifth generation mutants
• large abnormal vessels are present in the induced tumors of fifth generation mutants
• the volume of binucleated cardiomyocytes is increased by 24% in second generation mutants and 52% in fifth generation mutants
• the volume of mononucleated cardiomyocytes is increased by 39% and 43% in second and fifth generation mutants, respectively
• cardiomyocyte number is decreased 16% and 49% in second and fifth generation mutants, respectively
• heart weight is decreased in fifth generation mutants
• left ventricle weight is decreased in fifth generation mutants
• fifth generation mutants exhibit cardiac myocyte hypertrophy
• fifth generation mutants show a reduction in left ventricle mass that is accompanied by a decrease in left ventricle mass:chamber volume ratio, indicating decompensated eccentric left ventricle hypertrophy in the absence of an absolute increase in ventricular weight
• fifth generation, but not second generation, mutants suffer from a severe left ventricular failure
• dilated cardiomyopathy develops in fifth generation mutants
• fifth generation, but not second generation, mutants exhibit a decrease in +dP/dt
• fifth generation mutants exhibit a decrease in -dP/dt
• second and fifth generation mutants exhibit decreased cardiac myocyte proliferation
• fifth generation mutants exhibit a decrease in LV developed pressure
• fifth generation mutants exhibit an elevation of LV end-diastolic pressure
• fifth generation mutants exhibit a 63% increase in cardiomyocyte apoptosis
• older fifth generation mutants die of heart failure

hematopoietic system
• splenocytes from immunized fifth and sixth generation mice exhibit a small increase in apoptosis after mitogen treatment
• splenocytes (from both non-immunized and immunized) from sixth generation mutants show a decrease in the proliferative response to B and T cell mitogens
• splenocytes (from both non-immunized and immunized) from sixth generation mutants show a decrease in the proliferative response to B and T cell mitogens
• spleens from sixth generation mutants (but not earlier generations) show fewer follicles
• fifth and sixth generation homozygotes show a reduction in germinal centers following antigen (KLH) immunization

immune system
• splenocytes from immunized fifth and sixth generation mice exhibit a small increase in apoptosis after mitogen treatment
• splenocytes (from both non-immunized and immunized) from sixth generation mutants show a decrease in the proliferative response to B and T cell mitogens
• splenocytes (from both non-immunized and immunized) from sixth generation mutants show a decrease in the proliferative response to B and T cell mitogens
• spleens from sixth generation mutants (but not earlier generations) show fewer follicles
• fifth and sixth generation homozygotes show a reduction in germinal centers following antigen (KLH) immunization

embryo
• E10.5 embryos with neural tube defects exhibit an increase in apoptosis
• a portion of embryos with open neural tube show absence of bilateral symmetry in the brain
• a percentage of embryos fail to close the neural tube, particularly in the forebrain and midbrain, at E10.5; penetrance of this defect increases with generation number, with 30% of fifth generation embryos showing an open neural tube

nervous system
• a percentage of embryos fail to close the neural tube, particularly in the forebrain and midbrain, at E10.5; penetrance of this defect increases with generation number, with 30% of fifth generation embryos showing an open neural tube

reproductive system
• the number of oocytes that form synaptonemal complexes is decreased
• apoptosis is increased 5-fold in seminiferous tubules of G4 homozygotes; apoptosis is found in the outer layers of spermatocytes whereas the inner layer of spermatogonia remains intact
• in response to telomere shortening, male germ cells undergo apoptosis (J:89751)
• apoptotic depletion of germ cells in late generation mutants (J:120065)
• testicular atrophy and associated apoptotic depletion of germ cells in late generation mutants
• chromosome pairing, synapsis, and recombination are severely impaired in meiocytes with irregular telomeres
• in response to telomere shortening, female germ cells arrest in early meiosis
• meiocytes of fourth generation (G4) females with shortened telomeres bred with early generation males harboring relatively long telomeres, exhibit severely impaired chromosome pairing and synapsis and reduced meiotic recombination
• synaptonemal complex protein 3 (SCP3) elements are altered in G4 female meiotic cells
• the number of spermatocytes with synaptonemal complex protein 3 (SCP3) lateral elements is decreased in the fourth generation (G4) homozygotes
• late generation pregnant females have fewer fetuses
• mutants of late generations show a decrease in litter size
• Background Sensitivity: mutants are infertile at the sixth generation (of interbreeding) and infertile at the fourth generation of backcrossing to C57BL/6J

behavior/neurological
• older (6-8 months) fifth generation mutants often show a sudden decrease in activity

growth/size/body
• late generation mutants have reduced body size and are fragile
• late generation mutants have reduced body weight
• older (6-8 months) fifth generation mutants often show sudden losses in body weight
• 41% of homozygous fetuses from late generation pregnant females are reduced in size

muscle
• the volume of binucleated cardiomyocytes is increased by 24% in second generation mutants and 52% in fifth generation mutants
• the volume of mononucleated cardiomyocytes is increased by 39% and 43% in second and fifth generation mutants, respectively
• cardiomyocyte number is decreased 16% and 49% in second and fifth generation mutants, respectively
• fifth generation mutants show a reduction in left ventricle mass that is accompanied by a decrease in left ventricle mass:chamber volume ratio, indicating decompensated eccentric left ventricle hypertrophy in the absence of an absolute increase in ventricular weight
• dilated cardiomyopathy develops in fifth generation mutants
• fifth generation, but not second generation, mutants exhibit a decrease in +dP/dt
• fifth generation mutants exhibit a decrease in -dP/dt
• second and fifth generation mutants exhibit decreased cardiac myocyte proliferation
• fifth generation mutants exhibit a 63% increase in cardiomyocyte apoptosis

homeostasis/metabolism
N
• homozygotes exhibit normal wound healing
• first generation mutants are slightly less susceptible to DMBA + TPA induced skin tumorigenesis, with a delay in papilloma formation compared to wild-type and papillomas that do not progress to lesions bigger than 8 mm

digestive/alimentary system
• the GI crypts of late generation mutants exhibit high levels of apoptosis

skeleton
• late generation mutants exhibit kyphosis

integument
• late generation mutants exhibit alopecia

endocrine/exocrine glands
• testicular atrophy and associated apoptotic depletion of germ cells in late generation mutants




Genotype
MGI:4365574
hm4
Allelic
Composition
Terctm1Rdp/Terctm1Rdp
Genetic
Background
involves: FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• elongated spermatids from second generation (G2) homozygotes display variable telomere length, with some displaying long telomeres, while others have short telomeres
• at 8 months of age, second generation (G2) homozygotes exhibit fewer intact elongating spermatids containing extended telomeres than wild-type or heterozygous littermates
• however, fertility is preserved, suggesting that alternative telomere extension activity is capable of partially complementing the telomerase defect

reproductive system
• at 8 months of age, second generation (G2) homozygotes exhibit fewer intact elongating spermatids containing extended telomeres than wild-type or heterozygous littermates
• however, fertility is preserved, suggesting that alternative telomere extension activity is capable of partially complementing the telomerase defect




Genotype
MGI:5529018
cx5
Allelic
Composition
Dmdmdx-4Cv/Dmdmdx-4Cv
Terctm1Rdp/Terctm1Rdp
Genetic
Background
B6.Cg-Terctm1Rdp Dmdmdx-4Cv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dmdmdx-4Cv mutation (3 available); any Dmd mutation (153 available)
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
• cardiomyocyte nuclear area is moderately reduced in hearts of second generation (G2) 32 week old males as compared to controls
• cardiomyocyte diameter is smaller in hearts of 32 week old G2 males
• hearts from G2 males exhibit a loss of thick and thin myofilaments
• left ventricle enlargement is observed by 32 weeks in hearts of G2 males as compared to controls
• increased chamber size is observed in 32 week old G2 males as compared to controls
• left ventricular transverse area is increased in diastole and systole in G2 males
• ventricular fibrosis is observed by 32 weeks in hearts of G2 males
• reduced cardiac function is observed in older G1 males (80 weeks), but is not observed at 32 weeks
• cardiac dysfunction is observed at 8 weeks in third generation males
• cardiac dysfunction can be induced by angiotension II infusion in younger second generation males
• 32 week old G2 males exhibit reduced ventricular contractility as assessed by a reduction in fractional shortening as compared to controls
• wide QRS interval is observed in both G1 and G2 males as compared to controls

cellular
• 50% reduction in telomere length in G2 cardiomyocytes as compared to controls
• however, telomere lengths are similar to controls in vascular smooth muscle cells
• lack of well-defined cristae observed in cardiac muscle of second generation mice
• extensive mitochondrial fragmentation observed in cardiac muscle of second generation mice
• mitochondria size is decreaseed in cardiac muscle of second generation mice
• moderately increased number of mitochondria is observed in cardiac muscle of second generation mice
• an increased number of 8-OHdg-positive nuclei, a marker of oxidative damage, is observed in G2 hearts as compared to controls

mortality/aging
• death occurs as early as 30 weeks in first generation males, T50 is 120 weeks
• death occurs as early as 19 weeks in second generation males, T50 is 80 weeks

muscle
• cardiomyocyte nuclear area is moderately reduced in hearts of second generation (G2) 32 week old males as compared to controls
• cardiomyocyte diameter is smaller in hearts of 32 week old G2 males
• hearts from G2 males exhibit a loss of thick and thin myofilaments
• reduced cardiac function is observed in older G1 males (80 weeks), but is not observed at 32 weeks
• cardiac dysfunction is observed at 8 weeks in third generation males
• cardiac dysfunction can be induced by angiotension II infusion in younger second generation males
• 32 week old G2 males exhibit reduced ventricular contractility as assessed by a reduction in fractional shortening as compared to controls

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Duchenne muscular dystrophy DOID:11723 OMIM:310200
J:200365




Genotype
MGI:5556401
cx6
Allelic
Composition
Terctm1Rdp/Terctm1Rdp
Tinf2tm2.2Tdl/Tinf2+
Genetic
Background
involves: 129 * BALB/cJ * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
Tinf2tm2.2Tdl mutation (0 available); any Tinf2 mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• increase in chromosome ends without telomeric signals or signal loss from one of two sisters
• telomeres in bone marrow are shorter than homozygous Terctm1Rdp controls
• class of telomeres shorter than 15 kb is increased, while subfraction of longer telomeres is decreased




Genotype
MGI:2677844
cx7
Allelic
Composition
Terctm1Rdp/Terctm1Rdp
Terf1tm1Tdl/Terf1tm1Tdl
Genetic
Background
involves: 129S2/SvPas
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
Terf1tm1Tdl mutation (0 available); any Terf1 mutation (27 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• no homozygotes were born




Genotype
MGI:4820641
cx8
Allelic
Composition
Pms2tm1Lisk/Pms2tm1Lisk
Terctm1Rdp/Terctm1Rdp
Genetic
Background
involves: 129/Sv * 129S2/SvPas * C57BL/6 * C57BL/6J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pms2tm1Lisk mutation (1 available); any Pms2 mutation (11 available)
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
N
• mice exhibit increased survival compared with single homozygotes

neoplasm
• mice exhibit increased incidence of lymphomas compared with Terctm1Rdp homozygotes
• incidence of lymphomas decreases in successive generations
• mice exhibit increased incidence of carcinomas compared with Terctm1Rdp homozygotes
• however, the incidence of carcinomas after three generations is normal
• mice exhibit increased incidence of histiocytic sarcomas compared with Terctm1Rdp homozygotes
• however, the incidence of histiocytic sarcomas after three generations is normal

cellular
• telomeres in mouse embryonic fibroblasts or from small intestine sections become progressively shorter each generation compared to in cells from Terctm1Rdp homozygotes
• independent of telomere length, mouse embryonic fibroblasts (MEFs) undergo immortalization after fewer passages compared with cells from Terctm1Rdp homozygotes
• sister chromatid exchange in mouse embryonic fibroblasts is increased compared to in wild-type cells
• cells from the small intestine exhibit an increase in gamma-H2AX foci, indicative of DNA damage, compared with cells from wild-type mice
• compared with wild-type mice and third generation Terctm1Rdp homozygotes
• mouse embryonic fibroblasts (MEFs) exhibit fewer chromosomal breaks and fragmentations compared with MEFs from Pms2tm1Lisk
• MEFs exhibit in increase in microsatellite instability compared with wild-type cells
• end-to-end chromosome fusions in MEFs are increased compared to in cells from wild-type mice and Terctm1Rdp homozygotes
• however, mice exhibit rescue of increased bivalent recombination figures and chromatid cross-links observed in cells from Terctm1Rdp homozygotes and partial rescue of the complex chromosome aberrations, chromosomes fusions, and minichromosomes observed in cells from Pms2tm1Lisk homozygotes

digestive/alimentary system
N
• unlike in Terctm1Rdp homozygotes, proliferation of intestinal cells is rescued after 2 generations
• compared with wild-type mice and third generation Terctm1Rdp homozygotes
• mice exhibit reduced intestinal atrophy compared with Terctm1Rdp homozygotes

homeostasis/metabolism
• cells from the small intestine exhibit an increase in gamma-H2AX foci, indicative of DNA damage, compared with cells from wild-type mice




Genotype
MGI:3831883
cx9
Allelic
Composition
Pot1btm1.1Schg/Pot1btm1.1Schg
Terctm1Rdp/Terctm1Rdp
Genetic
Background
involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pot1btm1.1Schg mutation (0 available); any Pot1b mutation (27 available)
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• near complete absence of germ cells representing all stages of spermatogenesis

mortality/aging
• all mice but one mouse born alive died within days of birth
• the single exception died by P13, all additional phenotype data is for this single mouse

reproductive system
• near complete absence of germ cells representing all stages of spermatogenesis
• near complete absence of all stages of spermatogenesis

hematopoietic system
• striking absence of bone marrow cells
• acute bone marrow failure
• severe

digestive/alimentary system
• increased intestinal apoptosis

immune system




Genotype
MGI:3831884
cx10
Allelic
Composition
Pot1btm1.1Schg/Pot1btm1.1Schg
Terctm1Rdp/Terc+
Genetic
Background
involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pot1btm1.1Schg mutation (0 available); any Pot1b mutation (27 available)
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• overall median life span is 180 days
• median life span in males is 196 days while median life span for females is 84 days

cellular
• male germ cell depletion
• 3 fold decrease in testicular volume by 170 days of age
• phenotype is more severe than in mice homozygous for the Pot1b mutation alone
• increased apoptosis in proliferative tissues and cells (male germ cells, hematopoietic cells, intestinal cells)

reproductive system
• male germ cell depletion
• 3 fold decrease in testicular volume by 170 days of age
• phenotype is more severe than in mice homozygous for the Pot1b mutation alone
• testicular atrophy
• phenotype is more severe than in mice homozygous for the Pot1b mutation alone
• near complete absence of all stages of spermatogenesis by 170 days of age

hematopoietic system
• primary bone marrow cells and splenocytes show increased numbers of fused chromosomes, significantly shorter telomeres, and increased numbers of signal free ends
• 8 fold increase in apoptotic cells
• seen in females by 79 days of age
• bone marrow shows a striking absence of trilineage hematopoiesis
• striking decrease in the size and number of colonies of myeloid cells formed by bone marrow cells
• bone marrow shows a striking absence of trilineage hematopoiesis which is almost completely replaced by stromal adipose tissue
• acute bone marrow failure
• erythroid cells are reduced about 2 fold
• granulocytes present are left-shifted with dysplatic features and immature blasts are present
• mature granulocytes are reduced about 4 fold
• seen in females by 79 days of age
• by 79 days of age females develop severe leukopenia
• 60% of mice present with peripheral blood smears essentially devoid of leukocytes
• results suggest renewal of hematopoietic stem cells is severely impaired

pigmentation
• with age mice develop hyperpigmentation around their tails, legs, paws, and snout
• phenotype is more severe than in mice homozygous for the Pot1b mutation alone

growth/size/body
• both sexes weigh less than littermate controls
• phenotype is more severe than in mice homozygous for the Pot1b mutation alone

digestive/alimentary system
• about a 25 fold increase in apoptotic cells in the intestinal crypt
• increase in apoptosis is accompanied by an increase in the anaphase bridge index

endocrine/exocrine glands
• about a 25 fold increase in apoptotic cells in the intestinal crypt
• increase in apoptosis is accompanied by an increase in the anaphase bridge index
• testicular atrophy
• phenotype is more severe than in mice homozygous for the Pot1b mutation alone

immune system
• granulocytes present are left-shifted with dysplatic features and immature blasts are present
• mature granulocytes are reduced about 4 fold
• by 79 days of age females develop severe leukopenia
• 60% of mice present with peripheral blood smears essentially devoid of leukocytes

integument
• nail dystrophy
• phenotype is more severe than in mice homozygous for the Pot1b mutation alone

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
dyskeratosis congenita DOID:2729 OMIM:PS127550
J:144553




Genotype
MGI:3700822
cx11
Allelic
Composition
Terctm1Rdp/Terctm1Rdp
Wrntm1Lgu/Wrntm1Lgu
Genetic
Background
involves: 129/Sv * BALB/c * C57BL/6 * SLJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
Wrntm1Lgu mutation (1 available); any Wrn mutation (7 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• fourth to sixth generation (G4-G6) mutants have shorter median survival times than Terc homozygotes (24 weeks vs. 78 weeks)
• however, first and second generation (G1-G2) mutants have normal appearance, weight gain and lifespan
• 12- to 16-week old fourth to sixth generation (G4-G6) mutants have clinical features of premature aging

growth/size/body
• fourth to sixth generation (G4-G6) mutants have lower body weights, with a 20% reduction at 4 weeks of age and a 30% reduction at 32 weeks of age

cellular
• MEFs from G5 mutants exhibit an increase in chromosomal structural aberrations
• bone marrow metaphases derived from prematurely aged G4-G6 mutants show marked genomic instability, manifesting as more chromosomal p-p, p-q, and q-q arm fusions, and nonreciprocal translocations
• prematurely aged G4-G6 mutants exhibit accelerated loss of telomere length in primary bone marrow

homeostasis/metabolism
• 10 of 12 prematurely aged 20-week old G4-G6 mutants develop type II diabetes based on elevated fasting blood glucose levels, abnormal glucose tolerance tests and increased endogenous insulin levels
• prematurely aged 20-week old G4-G6 mutants show incresed endogenous insulin levels
• prematurely aged 20-week old G4-G6 mutants show abnormal glucose tolerance tests
• 24-week old prematurely aged fifth generation mutants show delayed wound closure
• 24-week old prematurely aged fifth generation mutants show impaired healing of acute wounds, with delayed wound closure and fewer proliferating cells at the sites of wound re-epithelialization

skeleton
• by 32 weeks of age, all G4-G6 mutants showing signs of premature aging have femoral bones with decreased cortical thickness and trabecular mass
• G1-G3 mutants routinely succumb to osteosarcomas and soft tissue sarcomas at around 63 weeks of age
• by 32 weeks of age, all G4-G6 mutants showing signs of premature aging have hunched spines
• increase in bone marrow fat content in young and aged mice
• 47.6% and 69.8% decrease in femur bone volume at 3 months of age and in aged mice, respectively
• 19% and 60.1% increase in cortical porosity in young and aged mice, respectively
• cortical bone area decreases with age, with a 29.7% decrease in aged mice
• by 32 weeks of age, all G4-G6 mutants showing signs of premature aging have femoral bones with decreased cortical thickness (J:91715)
• decrease in cortical thickness in both young and aged mice (J:213181)
• young femurs show a more rod-like trabecular structure
• increase in trabecular separation
• by 32 weeks of age, all G4-G6 mutants showing signs of premature aging have femoral bones with decreased trabecular mass
• decrease in trabecular thickness that begins in young age and progresses with age
• a proportion of G4-G6 mutants develop early-onset osteoporosis (J:91715)
• accelerated bone aging with characteristic features of human senile osteoporosis (J:213181)
• osteoid significantly decreases with age
• bone shows mechanical alterations including an increase in structure model index, a decrease in anisotropy and a decrease in the moment of inertia
• mineralized surface, mineral apposition rate, and bone formation rate dramatically decline with age
• by 32 weeks of age, all G4-G6 mutants showing signs of premature aging have bone fractures

vision/eye
• 12- to 16-week old f G4-G6 mutants develop cataracts

reproductive system
• 12- to 16-week old G4-G6 mutants show severe hypogonadism
• 20-week old G4-G6 mutants have small testes

neoplasm
• although prematurely aged G4-G6 mutants are not prominently cancer-prone (as they die prematurely), G1-G3 mutants routinely succumb to osteosarcomas and soft tissue sarcomas at around 63 weeks of age
• G1-G3 mutants routinely succumb to osteosarcomas and soft tissue sarcomas at around 63 weeks of age

digestive/alimentary system
• late-generation mutants have an increase in intestinal crypt cell apoptosis compared to Terc homozygotes

endocrine/exocrine glands
• late-generation mutants have an increase in intestinal crypt cell apoptosis compared to Terc homozygotes
• 20-week old G4-G6 mutants have small testes

limbs/digits/tail
• by 32 weeks of age, all G4-G6 mutants showing signs of premature aging have femoral bones with decreased cortical thickness and trabecular mass

adipose tissue
• G4-G6 mutants exhibit a 43% reduction in subcutaneous adipose tissue at 4 months of age
• increase in bone marrow fat content in young and aged mice

integument
• G4-G6 mutants exhibit a 43% reduction in subcutaneous adipose tissue at 4 months of age
• 12- to 16-week old G4-G6 mutants exhibit hair loss

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
osteoporosis DOID:11476 OMIM:166710
J:213181
Werner syndrome DOID:5688 OMIM:277700
J:91715




Genotype
MGI:3700845
cx12
Allelic
Composition
Terctm1Rdp/Terctm1Rdp
Tg(KRT5-Tert)8043Blas/0
Genetic
Background
involves: 129/Sv * C57BL/6 * C57BL/6J * DBA/2 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
Tg(KRT5-Tert)8043Blas mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• mutants exhibit an increase in the frequency of chromosome aberrations in keratinocytes, in particular, of end-to-end fusions, breaks, and telomere associations
• keratinocytes exhibit a significant decrease in average telomere length compared with wild-type cells, similar to that seen in mutant Terc homozygotes

homeostasis/metabolism
• mutants are less susceptible to DMBA + TPA induced skin tumorigenesis, with only 40% developing papillomas compared to 80%, 72% and 86% of wild-type, Tg(KRT5-Tert)8043Blas mutants, and Terc homozygous mutants, respectively
• the number of papillomas per mouse at week 15 is reduced compared to the above controls and papillomas never progress to lesions larger than 3 mm
• mutants exhibit a delayed rate of wound healing in skin compared to Tg(KRT5-Tert)8043Blas mutants

neoplasm
• mutants are less susceptible to DMBA + TPA induced skin tumorigenesis, with only 40% developing papillomas compared to 80%, 72% and 86% of wild-type, Tg(KRT5-Tert)8043Blas mutants, and Terc homozygous mutants, respectively
• the number of papillomas per mouse at week 15 is reduced compared to the above controls and papillomas never progress to lesions larger than 3 mm




Genotype
MGI:6258421
cx13
Allelic
Composition
Terctm1Rdp/Terctm1Rdp
Tg(KRT5-Terf2)PMBlas/Y
Genetic
Background
involves: 129/Sv * C57BL/6 * CBA * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
Tg(KRT5-Terf2)PMBlas mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
• double mutant mice exhibit more severe hair loss in light-exposed areas than age-matched single Tg(KRT5-Terf2)PMBlas mutant mice
• double mutant mice exhibit more severe skin dryness in light-exposed areas than age-matched single Tg(KRT5-Terf2)PMBlas mutant mice

cellular
• double mutant mice exhibit significantly shorter telomeres in tail skin than either single Tg(KRT5-Terf2)PMBlas mutant mice or single Terctm1Rdp homozygotes




Genotype
MGI:4936867
cx14
Allelic
Composition
Dmdmdx/Y
Terctm1Rdp/Terc+
Genetic
Background
involves: 129/Sv * C57BL/6J * C57BL/10ScSn * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dmdmdx mutation (32 available); any Dmd mutation (153 available)
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
muscle
• diaphragms exhibit increased diameter compared with control mice
• muscle stem cell proliferation in undamaged muscles is higher than in control mice

homeostasis/metabolism




Genotype
MGI:4936865
cx15
Allelic
Composition
Dmdmdx/Y
Terctm1Rdp/Terctm1Rdp
Genetic
Background
involves: 129/Sv * C57BL/6J * C57BL/10ScSn * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dmdmdx mutation (32 available); any Dmd mutation (153 available)
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• second generation mice beginning at 48 weeks of age likely due to respiratory failure

muscle
• first and second generation mice exhibit a progressive reduction in revertant myofiber cluster size compared to in control mice
• at 8 weeks in second generation mice
• at 8 weeks in second generation mice
• in first and second generation mice
• diaphragms in first and second generation mice exhibit increased diameter compared with control mice
• by 76 weeks, diaphragm muscle is atrophied unlike in control mice
• in aged second generation mice
• in second generation mice with age
• in second generation mice
• second generation mice exhibit calcium depositions in the muscles unlike control mice
• second generation mice exhibit progressive muscular dystrophy with age unlike control mice
• however, dystrophic phenotypes are improved by transplantation with wild-type muscle stem cells
• in first and second generation mice prior to and after damage
• at 8 weeks, second generation mice exhibit increased myofiber membrane permeability compared with control mice
• second generation mice exhibit impaired muscle stem cell proliferation compared with control mice
• muscle stem cells from second generation mice exhibit impaired proliferative potential in culture compared with control cells
• muscle stem cells from second generation mice exhibit impaired engrafting after transplantation compared with control cells
• at 8 weeks in second generation mice
• at 8 weeks, first and second generation mice exhibit decreased muscle twitch force, tetanic force, and tetanic tension compared with control mice
• at 8 weeks, second generation mice spend less time running on a treadmill than control mice
• at 8 weeks, second generation mice hold onto a grid for less time than control mice

homeostasis/metabolism
• at 8 weeks, second generation mice spend less time running on a treadmill than control mice
• at 8 weeks in second generation mice, but declining after 60 weeks of age

cellular
• myoblasts from first and second generation exhibit shortened telomeres compared with control cells
• at 8 weeks in second generation mice
• myoblasts from first and second generation exhibit fused chromosomes unlike control cells

skeleton
• in aged second generation mice

respiratory system
• second generation mice beginning at 48 weeks of age likely due to respiratory failure

immune system
• at 8 weeks in second generation mice

behavior/neurological
• at 8 weeks, second generation mice spend less time running on a treadmill than control mice

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Duchenne muscular dystrophy DOID:11723 OMIM:310200
J:167294




Genotype
MGI:3719052
cx16
Allelic
Composition
Cdkn2atm1Rdp/Cdkn2atm1Rdp
Terctm1Rdp/Terctm1Rdp
Genetic
Background
involves: 129/Sv * C57BL/6J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm1Rdp mutation (6 available); any Cdkn2a mutation (52 available)
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Degenerative phenotypes, including increased apoptosis in gastrointestinal crypts and germ cell depletion, in Terctm1Rdp/Terctm1Rdp and Cdkn2atm1Rdp/Cdkn2atm1Rdp Terctm1Rdp/Terctm1Rdp mice

mortality/aging
• 12- to 13-week old late generation (G4) mutants exhibit accelerated degeneration as indicated by hair graying, alopecia, kyphosis, reduced body size and weight, and fragility

neoplasm
• 98% of early generation mutants succumb to tumors with a median tumor-free latency of 38.6 weeks
• late generation mutants show a decrease in percent tumor death and an increase in tumor-free latency, from 98% to 43% and 38.6-65.3 weeks compared to early generation mutants
• 11% and 10% of early generation and late generation mutants, respectively, develop lymphomas
• 57% and 59% of early generation and late generation mutants, respectively, develop histocytic sarcomas
• 24% and 28% of early generation and late generation mutants, respectively, develop soft tissue sarcomas

cellular
• the anaphase bridge index (ABI) is increased to the same extent as in Terctm1Rdp homozygotes in late-generation (G4/G5) intestinal crypts indicating telomere dysfunction
• apoptotic depletion of germ cells in late generation mutants
• MEFs grown in culture show decreased growth rates after 10 population doublings with steady slow proliferation thereafter, indicating that telomere dysfunction suppresses the growth rate
• early generation (G0) astrocytes show continuous proliferation whereas the late generation (G4) astrocytes senesce after 2.5 population doublings, indicating that telomere dysfunction constrains the immortalization potential of astrocytes

reproductive system
• apoptotic depletion of germ cells in late generation mutants
• testicular atrophy and associated apoptotic depletion of germ cells in late generation mutants

growth/size/body
• late generation mutants have reduced body size and are fragile
• late generation mutants have reduced body weight

digestive/alimentary system
• the GI crypts of late generation mutants exhibit high levels of apoptosis

skeleton
• late generation mutants exhibit kyphosis

endocrine/exocrine glands
• testicular atrophy and associated apoptotic depletion of germ cells in late generation mutants




Genotype
MGI:3719054
cx17
Allelic
Composition
Cdkn2atm1Rdp/Cdkn2a+
Terctm1Rdp/Terctm1Rdp
Genetic
Background
involves: 129/Sv * C57BL/6J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2atm1Rdp mutation (6 available); any Cdkn2a mutation (52 available)
Terctm1Rdp mutation (4 available); any Terc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• 84% of early generation mutants succumb to tumors with a median tumor-free latency of 71.6 weeks
• late generation mutants show a decrease in percent tumor death and an increase in tumor-free latency, from 84% to 20% and 71.6-104.9 weeks
• 19% and 23% of early generation and late generation mutants, respectively, develop lymphomas
• 35% and 39% of early generation and late generation mutants, respectively, develop histocytic sarcomas
• 20% and 23% of early generation and late generation mutants, respectively, develop soft tissue sarcomas





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last database update
05/26/2020
MGI 6.15
The Jackson Laboratory