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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Sirt1tm1Mcby
targeted mutation 1, Michael W McBurney
MGI:2448246
Summary 5 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Sirt1tm1Mcby/Sirt1tm1Mcby 129/Sv-Sirt1tm1Mcby MGI:4361352
hm2
Sirt1tm1Mcby/Sirt1tm1Mcby involves: 129 MGI:3783470
hm3
Sirt1tm1Mcby/Sirt1tm1Mcby involves: 129S1/Sv * 129X1/SvJ MGI:4456087
hm4
Sirt1tm1Mcby/Sirt1tm1Mcby involves: 129S1/Sv * 129X1/SvJ * CD-1 MGI:3783471
cx5
Actbtm3.1(Sirt1)Npa/Actb+
Sirt1tm1Mcby/Sirt1tm1Mcby
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J MGI:4456088


Genotype
MGI:4361352
hm1
Allelic
Composition
Sirt1tm1Mcby/Sirt1tm1Mcby
Genetic
Background
129/Sv-Sirt1tm1Mcby
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sirt1tm1Mcby mutation (2 available); any Sirt1 mutation (51 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• after 14-18 backcrosses on a 129/Sv background, most homozygotes die at around 3 or 4 weeks of age; only rare homozygotes survive up to 6 weeks of age
• Background Sensitivity: unlike homozygotes that are backcrossed on a 129/Sv strain, homozygotes generated on a C57BL/6 background or an outbred background involving 129/Sv and CD-1 can survive into adulthood

reproductive system
N
• at postnatal day 1 (P1), neonatal male homozygotes display normal fetal testis, Leydig cell, and Sertoli cell development relative to wild-type controls
• in addition, spermatogonial multiplication and stem cell renewal appear unaffected
• at 3 weeks of age, male homozygotes show severely reduced numbers or a total absence of spermatids
• at 3 weeks of age, male homozygotes display numerous multinucleate or abnormally large spermatocytes in the seminiferous tubules, indicating degenerating or dying spermatocytes
• at 3 weeks of age, TUNEL analysis indicates abundant apoptosis of pachytene spermatocytes
• at 3 weeks of age, only 3% of mutant seminiferous tubules exhibit a tubular lumen vs 99% of wild-type tubules
• at 3 weeks of age, male homozygotes display a severely reduced number of developing adult-type Leydig cells relative to wild-type controls
• at 3 weeks of age, mutant testes show absence of differentiating Leydig cells with an oval-to-round-shaped nucleus morphology, typical of maturing wild-type Leydig cells
• instead, clusters of fetal-type Leydig cells and some early spindle-shaped progenitor cells are found close to the seminiferous tubules and blood vessels
• at 3 weeks of age, the average mutant seminiferous tubular diameter is reduced ~40% relative to the wild-type
• at 3 weeks of age, mutant Sertoli cell nuclei often contain several smaller nucleoli instead of one single nucleolus, indicating defective Sertoli cell maturation
• at P27, male homozygotes display a >5-fold decrease in intratesticular testosterone levels relative to wild-type controls
• Background Sensitivity: unlike homozygotes that are backcrossed on a 129/Sv strain, homozygotes generated on a C57BL/6 background or an outbred background involving 129/Sv and CD-1 display defective rather than arrested spermatogenesis
• the first round of spermatogenesis arrests in late-meiotic prophase; as a result, only rare round spermatids are observed
• however, germ cell proliferation is not significantly decreased
• male infertility is attributed to dysregulated hypothalamic-pituitary gonadotropin signaling

endocrine/exocrine glands
• at 3 weeks of age, only 3% of mutant seminiferous tubules exhibit a tubular lumen vs 99% of wild-type tubules
• at 3 weeks of age, male homozygotes display a severely reduced number of developing adult-type Leydig cells relative to wild-type controls
• at 3 weeks of age, mutant testes show absence of differentiating Leydig cells with an oval-to-round-shaped nucleus morphology, typical of maturing wild-type Leydig cells
• instead, clusters of fetal-type Leydig cells and some early spindle-shaped progenitor cells are found close to the seminiferous tubules and blood vessels
• at 3 weeks of age, the average mutant seminiferous tubular diameter is reduced ~40% relative to the wild-type
• at 3 weeks of age, mutant Sertoli cell nuclei often contain several smaller nucleoli instead of one single nucleolus, indicating defective Sertoli cell maturation
• at P27, male homozygotes display a >5-fold decrease in intratesticular testosterone levels relative to wild-type controls

growth/size/body
• at 3 weeks of age, male homozygotes are significantly smaller than wild-type controls
• at 3 weeks of age, male homozygotes display a severely reduced growth relative to wild-type controls

homeostasis/metabolism
• at P12, serum FSH levels in mutant male mice are reduced by ~50% relative to wild-type levels
• at 3 weeks of age, serum LH leves in mutant male mice are below the detection limit of the RIA

cellular
• at 3 weeks of age, male homozygotes show severely reduced numbers or a total absence of spermatids
• at 3 weeks of age, male homozygotes display numerous multinucleate or abnormally large spermatocytes in the seminiferous tubules, indicating degenerating or dying spermatocytes
• at 3 weeks of age, TUNEL analysis indicates abundant apoptosis of pachytene spermatocytes




Genotype
MGI:3783470
hm2
Allelic
Composition
Sirt1tm1Mcby/Sirt1tm1Mcby
Genetic
Background
involves: 129
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sirt1tm1Mcby mutation (2 available); any Sirt1 mutation (51 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
muscle
• occurs as a result of lung inflammation

mortality/aging
• only half the expected number of homozygotes are found one day after birth
• the expected Mendelian ratio is observed in E18.5 embryos indicating the pups die shortly before or after birth
• all mice die within one month of birth

embryo
• embryos are visibly smaller than controls starting at E12.5

growth/size/body
• occurs as a result of lung inflammation
• many mice have a short or deviated snout
• embryos are visibly smaller than controls starting at E12.5
• mice weigh smaller at birth compared to wild-type littermates and continue to be under weight until their premature death

vision/eye
• in some mice the eyes are smaller possibly as result of failure of eyelids to open
• eyelids remain closed for entire lifespan

respiratory system
• frequently observed in mice
• lungs are infiltrated with neutrophils suggesting chronic pulmonary infection
• occurs consistently in mice

hematopoietic system
• there is a decreased number of CD8 T cells in the spleen

craniofacial
• many mice have a short or deviated snout

homeostasis/metabolism
• frequently observed in mice

cardiovascular system
• occurs as a result of lung inflammation

digestive/alimentary system
• the pancreas shows patchy atrophy of the exocrine epithelium

limbs/digits/tail
• mineralization of digits is delayed relative to their wild-type littermates

endocrine/exocrine glands
• the pancreas shows patchy atrophy of the exocrine epithelium

immune system
• there is a decreased number of CD8 T cells in the spleen
• lungs are infiltrated with neutrophils suggesting chronic pulmonary infection
• occurs consistently in mice




Genotype
MGI:4456087
hm3
Allelic
Composition
Sirt1tm1Mcby/Sirt1tm1Mcby
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sirt1tm1Mcby mutation (2 available); any Sirt1 mutation (51 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
(J:160212)
(J:241633)
(J:160212)
(J:241633)

behavior/neurological

craniofacial
• rugae of the hard palate are disorganized

growth/size/body
• rugae of the hard palate are disorganized

digestive/alimentary system
• rugae of the hard palate are disorganized
• lymphoid infiltration of salivary gland in almost all mice; infiltration is more extensive than in Sirt1tm3.1 mice

vision/eye
• lymphoid infiltration of lacrimal gland in almost all mice; infiltration is more extensive than in Sirt1tm3.1 mice
• interorbital distance is reduced

endocrine/exocrine glands
• lymphoid infiltration of salivary gland in almost all mice; infiltration is more extensive than in Sirt1tm3.1 mice
• lymphoid infiltration of lacrimal gland in almost all mice; infiltration is more extensive than in Sirt1tm3.1 mice

immune system
• increased levels of La and Ro autoantibodies

mortality/aging
• high levels of perinatal lethality

respiratory system
• elevated respiration




Genotype
MGI:3783471
hm4
Allelic
Composition
Sirt1tm1Mcby/Sirt1tm1Mcby
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sirt1tm1Mcby mutation (2 available); any Sirt1 mutation (51 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
muscle
• occurs as a result of lung inflammation

mortality/aging
• only half the expected number of homozygotes are found one day after birth
• the expected Mendelian ratio is observed in E18.5 embryos indicating the pups die shortly before or after birth

embryo
• embryos are visibly smaller than controls starting at E12.5

reproductive system
• there are 20-fold less mature sperm in the seminal fluid compared to wild-type littermates
• majority of sperm are abnormal with small, rounded cell bodies and blunted or absent hooks in the tail
• many of the sperm have flagellas that are fine and lack associated cell bodies
• many sperm retain cytoplasm around their nucleus
• majority of sperm are abnormal with small, rounded cell bodies
• there are decreased number of mature spermatids and increased numbers of retained elongated spermatids in the testis of some mice
• multi-nucleated germ cells occasionally occur
• retention of highly condensed spermatids occurs in most mice with some spermatids sharing acrosomes and other being larger than normal
• all mice have increased levels of spermatocyte apoptosis
• virtually none of the mature sperm cells are motile
• corpora lutea are absent possibly due to failure to ovulate
• ovaries are smaller than wild-type littermates
• there is an increase in the number and size of vacuoles within the seminiferous epithelium
• testis are subnormal in weight
• uterus is thin walled
• ovaries from female mice are able to form follicles but fail to ovulate
• ovulation will occur after injections with gonadotropin and choriogonadotropin
• female mice are arrested in diestrus and do not ovulate
• defects in estrous cycle can be overcome by injections with gonadotropin and choriogonadotropin
• females do not appear to cycle efficiently through estrus
• only one female out of seven was able to produce offspring with a wild-type male
• male mice are unable to produce sire with wild-type females

growth/size/body
• occurs as a result of lung inflammation
• many mice have a short or deviated snout
• embryos are visibly smaller than controls starting at E12.5
• mice weigh smaller at birth compared to wild-type littermates and continue to be under weight well into adulthood
• starting at 30 days of age, many mice reach weights that is similar to controls
• mice are 25% smaller at 2-4 months of age
• as they get older, weight differences increase to 30% at 5-8 months of age and 40% at 13-20 months of age

vision/eye
• in some mice the eyes are smaller possibly as result of failure of eyelids to open
• eyelids remain closed for at least several months and sometimes for entire lifespan

craniofacial
• many mice have a short or deviated snout

endocrine/exocrine glands
• the pancreas shows patchy atrophy of the exocrine epithelium
• corpora lutea are absent possibly due to failure to ovulate
• ovaries are smaller than wild-type littermates
• there is an increase in the number and size of vacuoles within the seminiferous epithelium
• testis are subnormal in weight
• insulin levels rise 3-fold higher than in wild-type mice in response to refeeding after overnight fast

respiratory system
• frequently observed in mice
• lungs are infiltrated with neutrophils suggesting chronic pulmonary infection
• occurs consistently in mice

behavior/neurological
• mice under a year in age comsume 20% more calories when normalized to body weight
• mice older than a year in age consume 46% more calories when normalized to bodyweight
• mice 3-6 months of age are 50% less active than controls with the biggest differences occurring during the dark phase
• older mice are about 33% less active than controls
• the female mouse able to produce offspring failed to nurse her pups

homeostasis/metabolism
• insulin levels rise 3-fold higher than in wild-type mice in response to refeeding after overnight fast
• circulating levels of thyroxine are 20% less than in controls
• frequently observed in mice
• mice have a 20% higher oxygen consumption as measured by percent relative cumulative frequency of VO2 normalized to body weight
• the largest differences occur during the light period when mice are inactive
• respiratory exchange ratios indicate that mice rely more on oxidation of fatty lipids during the 6-8 hours prior to onset of the dark period
• mice increase their oxygen consumption to a higher degree than in wild-type mice when on a calorie-restricted diet for over 25 weeks
• serum glucose levels in fasted mice are almost 30% lower than in wild-type mice
• upon refeeding, glucose levels increase to a level comparable to wild-type mice
• urine vasopressin concentration is increased
• several 18-22 month old mice excrete large volumes of urine with low osmolarity

limbs/digits/tail
• mineralization of digits is delayed relative to their wild-type littermates

digestive/alimentary system
• the pancreas shows patchy atrophy of the exocrine epithelium

cardiovascular system
• occurs as a result of lung inflammation

immune system
• there is a decreased number of CD8 T cells in the spleen
• sinusoids of the liver show deposits
• 73% of mice have anti-nuclear antibodies
• immunoglobulin deposits in the kidney
• lungs are infiltrated with neutrophils suggesting chronic pulmonary infection
• occurs consistently in mice

hematopoietic system
• there is a decreased number of CD8 T cells in the spleen
• sinusoids of the liver show deposits

adipose tissue
• inguinal fat pads are 34% smaller at 3-5 months of age and 52% smaller in mice between 1-2 years of age
• a calorie restricted diet for 25-28 weeks decreases fat pad weight to a higher degree than in wild-type mice

cellular
• there are 20-fold less mature sperm in the seminal fluid compared to wild-type littermates
• majority of sperm are abnormal with small, rounded cell bodies and blunted or absent hooks in the tail
• many of the sperm have flagellas that are fine and lack associated cell bodies
• many sperm retain cytoplasm around their nucleus
• majority of sperm are abnormal with small, rounded cell bodies
• there are decreased number of mature spermatids and increased numbers of retained elongated spermatids in the testis of some mice
• multi-nucleated germ cells occasionally occur
• retention of highly condensed spermatids occurs in most mice with some spermatids sharing acrosomes and other being larger than normal
• all mice have increased levels of spermatocyte apoptosis
• virtually none of the mature sperm cells are motile
• liver but not skeletal mitochondria produce less ATP and have a lower proton motive force under both phosphorylating and non-phosphorylating conditions
• liver mitochondria also produce less reactive oxygen species

nervous system
• the brain weight is 20% smaller in both younger and older mice

renal/urinary system
• urine vasopressin concentration is increased
• several 18-22 month old mice excrete large volumes of urine with low osmolarity
• the glomeruli of 24 month old animals are hypercellular with evidence of reduced vascularity
• immunoglobulin deposits in the kidney

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
nephrogenic diabetes insipidus DOID:12387 OMIM:125800
OMIM:304800
J:160869




Genotype
MGI:4456088
cx5
Allelic
Composition
Actbtm3.1(Sirt1)Npa/Actb+
Sirt1tm1Mcby/Sirt1tm1Mcby
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Actbtm3.1(Sirt1)Npa mutation (1 available); any Actb mutation (28 available)
Sirt1tm1Mcby mutation (2 available); any Sirt1 mutation (51 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• unlike Sirt1tm1Mcby homozygotes, mice are fertile

growth/size/body
N
• unlike Sirt1tm1Mcby homozygotes, mice exhibit normal body size and weight

vision/eye
N
• unlike Sirt1tm1Mcby homozygotes, eyelids open





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last database update
11/10/2020
MGI 6.16
The Jackson Laboratory