All Phenotypes Sirt1<tm1Mcby> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sirt1^tm1Mcby/Sirt1^tm1Mcby	129/Sv-Sirt1^tm1Mcby	MGI:4361352
hm2	Sirt1^tm1Mcby/Sirt1^tm1Mcby	involves: 129	MGI:3783470
hm3	Sirt1^tm1Mcby/Sirt1^tm1Mcby	involves: 129S1/Sv * 129X1/SvJ	MGI:4456087
hm4	Sirt1^tm1Mcby/Sirt1^tm1Mcby	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3783471
cx5	Actb^{tm3.1(Sirt1)Npa}/Actb⁺ Sirt1^tm1Mcby/Sirt1^tm1Mcby	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J	MGI:4456088

Allelic Composition	Sirt1^tm1Mcby/Sirt1^tm1Mcby
Genetic Background	129/Sv-Sirt1^tm1Mcby

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sirt1^tm1Mcby mutation (2 available); any Sirt1 mutation (81 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:146009 )

• 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

reproductive system phenotype ( J:146009 )

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

abnormal spermatid morphology ( J:146009 )

• at 3 weeks of age, male homozygotes show severely reduced numbers or a total absence of spermatids

abnormal spermatocyte morphology ( J:146009 )

• at 3 weeks of age, male homozygotes display numerous multinucleate or abnormally large spermatocytes in the seminiferous tubules, indicating degenerating or dying spermatocytes

multinucleated giant male germ cells ( J:146009 )

increased male germ cell apoptosis ( J:146009 )

• at 3 weeks of age, TUNEL analysis indicates abundant apoptosis of pachytene spermatocytes

abnormal seminiferous tubule morphology ( J:146009 )

• at 3 weeks of age, only 3% of mutant seminiferous tubules exhibit a tubular lumen vs 99% of wild-type tubules

small seminiferous tubules ( J:146009 )

• at 3 weeks of age, the average mutant seminiferous tubular diameter is reduced ~40% relative to the wild-type

abnormal Sertoli cell development ( J:146009 )

• at 3 weeks of age, mutant Sertoli cell nuclei often contain several smaller nucleoli instead of one single nucleolus, indicating defective Sertoli cell maturation

abnormal adult Leydig cell differentiation ( J:146009 )

• 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

decreased Leydig cell number ( J:146009 )

• at 3 weeks of age, male homozygotes display a severely reduced number of developing adult-type Leydig cells relative to wild-type controls

decreased testes secretion ( J:146009 )

• at P27, male homozygotes display a >5-fold decrease in intratesticular testosterone levels relative to wild-type controls

arrest of spermatogenesis ( J:146009 )

arrest of male meiosis ( J:146009 )

• 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 ( J:146009 )

• male infertility is attributed to dysregulated hypothalamic-pituitary gonadotropin signaling

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:146009 )

• at 3 weeks of age, only 3% of mutant seminiferous tubules exhibit a tubular lumen vs 99% of wild-type tubules

small seminiferous tubules ( J:146009 )

• at 3 weeks of age, the average mutant seminiferous tubular diameter is reduced ~40% relative to the wild-type

abnormal Sertoli cell development ( J:146009 )

• at 3 weeks of age, mutant Sertoli cell nuclei often contain several smaller nucleoli instead of one single nucleolus, indicating defective Sertoli cell maturation

abnormal adult Leydig cell differentiation ( J:146009 )

• 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

decreased Leydig cell number ( J:146009 )

• at 3 weeks of age, male homozygotes display a severely reduced number of developing adult-type Leydig cells relative to wild-type controls

decreased testes secretion ( J:146009 )

• at P27, male homozygotes display a >5-fold decrease in intratesticular testosterone levels relative to wild-type controls

growth/size/body

decreased body size ( J:146009 )

• at 3 weeks of age, male homozygotes are significantly smaller than wild-type controls

postnatal growth retardation ( J:146009 )

• at 3 weeks of age, male homozygotes display a severely reduced growth relative to wild-type controls

homeostasis/metabolism

decreased circulating follicle stimulating hormone level ( J:146009 )

• at P12, serum FSH levels in mutant male mice are reduced by ~50% relative to wild-type levels

decreased circulating luteinizing hormone level ( J:146009 )

• at 3 weeks of age, serum LH leves in mutant male mice are below the detection limit of the RIA

cellular

abnormal spermatid morphology ( J:146009 )

• at 3 weeks of age, male homozygotes show severely reduced numbers or a total absence of spermatids

abnormal spermatocyte morphology ( J:146009 )

• at 3 weeks of age, male homozygotes display numerous multinucleate or abnormally large spermatocytes in the seminiferous tubules, indicating degenerating or dying spermatocytes

multinucleated giant male germ cells ( J:146009 )

arrest of male meiosis ( J:146009 )

• 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

increased male germ cell apoptosis ( J:146009 )

• at 3 weeks of age, TUNEL analysis indicates abundant apoptosis of pachytene spermatocytes

Allelic Composition	Sirt1^tm1Mcby/Sirt1^tm1Mcby
Genetic Background	involves: 129

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sirt1^tm1Mcby mutation (2 available); any Sirt1 mutation (81 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

postnatal lethality, complete penetrance ( J:81010 )

• all mice die within one month of birth

perinatal lethality, incomplete penetrance ( J:81010 )

• 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

decreased embryo size ( J:81010 )

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

growth/size/body

heart right ventricle hypertrophy ( J:81010 )

• occurs as a result of lung inflammation

short snout ( J:81010 )

• many mice have a short or deviated snout

decreased embryo size ( J:81010 )

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

decreased body weight ( J:81010 )

• mice weigh smaller at birth compared to wild-type littermates and continue to be under weight until their premature death

vision/eye

microphthalmia ( J:81010 )

• in some mice the eyes are smaller possibly as result of failure of eyelids to open

eyelids fail to open ( J:81010 )

• eyelids remain closed for entire lifespan

respiratory system

pulmonary edema ( J:81010 )

• frequently observed in mice

lung inflammation ( J:81010 )

• lungs are infiltrated with neutrophils suggesting chronic pulmonary infection

interstitial pneumonia ( J:81010 )

• occurs consistently in mice

hematopoietic system

decreased CD8-positive, alpha-beta T cell number ( J:81010 )

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

craniofacial

short snout ( J:81010 )

• many mice have a short or deviated snout

homeostasis/metabolism

pulmonary edema ( J:81010 )

• frequently observed in mice

cardiovascular system

heart right ventricle hypertrophy ( J:81010 )

• occurs as a result of lung inflammation

digestive/alimentary system

exocrine pancreas atrophy ( J:81010 )

• the pancreas shows patchy atrophy of the exocrine epithelium

limbs/digits/tail

abnormal digit development ( J:81010 )

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

endocrine/exocrine glands

exocrine pancreas atrophy ( J:81010 )

• the pancreas shows patchy atrophy of the exocrine epithelium

immune system

decreased CD8-positive, alpha-beta T cell number ( J:81010 )

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

lung inflammation ( J:81010 )

• lungs are infiltrated with neutrophils suggesting chronic pulmonary infection

interstitial pneumonia ( J:81010 )

• occurs consistently in mice

muscle

heart right ventricle hypertrophy ( J:81010 )

• occurs as a result of lung inflammation

Allelic Composition	Sirt1^tm1Mcby/Sirt1^tm1Mcby
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sirt1^tm1Mcby mutation (2 available); any Sirt1 mutation (81 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

reproductive system

female infertility ( J:160212 , J:241633 )

(J:160212)

(J:241633)

male infertility ( J:160212 , J:241633 )

(J:160212)

(J:241633)

behavior/neurological

lethargy ( J:241633 )

craniofacial

abnormal palatal rugae morphology ( J:241633 )

• rugae of the hard palate are disorganized

short snout ( J:241633 )

growth/size/body

abnormal palatal rugae morphology ( J:241633 )

• rugae of the hard palate are disorganized

short snout ( J:241633 )

decreased body size ( J:160212 , J:241633 )

decreased body weight ( J:160212 )

digestive/alimentary system

abnormal palatal rugae morphology ( J:241633 )

• rugae of the hard palate are disorganized

abnormal salivary gland morphology ( J:241633 )

• lymphoid infiltration of salivary gland in almost all mice; infiltration is more extensive than in Sirt1^tm3.1 mice

vision/eye

abnormal lacrimal gland morphology ( J:241633 )

• lymphoid infiltration of lacrimal gland in almost all mice; infiltration is more extensive than in Sirt1^tm3.1 mice

ocular hypotelorism ( J:241633 )

• interorbital distance is reduced

abnormal eyelid morphology ( J:241633 )

eyelids fail to open ( J:160212 )

endocrine/exocrine glands

abnormal salivary gland morphology ( J:241633 )

• lymphoid infiltration of salivary gland in almost all mice; infiltration is more extensive than in Sirt1^tm3.1 mice

abnormal lacrimal gland morphology ( J:241633 )

• lymphoid infiltration of lacrimal gland in almost all mice; infiltration is more extensive than in Sirt1^tm3.1 mice

immune system

increased autoantibody level ( J:241633 )

• increased levels of La and Ro autoantibodies

mortality/aging

perinatal lethality ( J:241633 )

• high levels of perinatal lethality

respiratory system

hyperpnea ( J:241633 )

• elevated respiration

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

muscle

heart right ventricle hypertrophy ( J:81010 )

• occurs as a result of lung inflammation

mortality/aging

perinatal lethality, incomplete penetrance ( J:81010 )

• 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

decreased embryo size ( J:81010 )

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

reproductive system

oligozoospermia ( J:81010 )

• there are 20-fold less mature sperm in the seminal fluid compared to wild-type littermates

teratozoospermia ( J:81010 )

• majority of sperm are abnormal with small, rounded cell bodies and blunted or absent hooks in the tail

abnormal sperm flagellum morphology ( J:81010 )

• many of the sperm have flagellas that are fine and lack associated cell bodies

globozoospermia ( J:81010 )

• many sperm retain cytoplasm around their nucleus

• majority of sperm are abnormal with small, rounded cell bodies

abnormal spermatid morphology ( J:81010 )

• 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

increased male germ cell apoptosis ( J:81010 )

• all mice have increased levels of spermatocyte apoptosis

immotile sperm ( J:81010 )

• virtually none of the mature sperm cells are motile

absent corpus luteum ( J:81010 )

• corpora lutea are absent possibly due to failure to ovulate

small ovary ( J:81010 )

• ovaries are smaller than wild-type littermates

abnormal seminiferous tubule epithelium morphology ( J:81010 )

• there is an increase in the number and size of vacuoles within the seminiferous epithelium

decreased testis weight ( J:81010 )

• testis are subnormal in weight

thin uterus ( J:81010 )

• uterus is thin walled

anovulation ( J:81010 )

• ovaries from female mice are able to form follicles but fail to ovulate

• ovulation will occur after injections with gonadotropin and choriogonadotropin

abnormal estrous cycle ( J:81010 )

• female mice are arrested in diestrus and do not ovulate

• defects in estrous cycle can be overcome by injections with gonadotropin and choriogonadotropin

absent estrous cycle ( J:81010 )

• females do not appear to cycle efficiently through estrus

reduced female fertility ( J:81010 )

• only one female out of seven was able to produce offspring with a wild-type male

male infertility ( J:81010 )

• male mice are unable to produce sire with wild-type females

growth/size/body

heart right ventricle hypertrophy ( J:81010 )

• occurs as a result of lung inflammation

short snout ( J:81010 )

• many mice have a short or deviated snout

decreased embryo size ( J:81010 )

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

decreased body weight ( J:81010 )

• 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

slow postnatal weight gain ( J:133127 )

• 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

microphthalmia ( J:81010 )

• in some mice the eyes are smaller possibly as result of failure of eyelids to open

eyelids fail to open ( J:81010 )

• eyelids remain closed for at least several months and sometimes for entire lifespan

craniofacial

short snout ( J:81010 )

• many mice have a short or deviated snout

endocrine/exocrine glands

exocrine pancreas atrophy ( J:81010 )

• the pancreas shows patchy atrophy of the exocrine epithelium

absent corpus luteum ( J:81010 )

• corpora lutea are absent possibly due to failure to ovulate

small ovary ( J:81010 )

• ovaries are smaller than wild-type littermates

abnormal seminiferous tubule epithelium morphology ( J:81010 )

• there is an increase in the number and size of vacuoles within the seminiferous epithelium

decreased testis weight ( J:81010 )

• testis are subnormal in weight

increased insulin secretion ( J:133127 )

• insulin levels rise 3-fold higher than in wild-type mice in response to refeeding after overnight fast

respiratory system

pulmonary edema ( J:81010 )

• frequently observed in mice

lung inflammation ( J:81010 )

• lungs are infiltrated with neutrophils suggesting chronic pulmonary infection

interstitial pneumonia ( J:81010 )

• occurs consistently in mice

behavior/neurological

polydipsia ( J:160869 )

polyphagia ( J:133127 )

• 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

decreased locomotor activity ( J:133127 )

• 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

abnormal nursing ( J:81010 )

• the female mouse able to produce offspring failed to nurse her pups

homeostasis/metabolism

increased insulin secretion ( J:133127 )

• insulin levels rise 3-fold higher than in wild-type mice in response to refeeding after overnight fast

decreased circulating thyroxine level ( J:133127 )

• circulating levels of thyroxine are 20% less than in controls

pulmonary edema ( J:81010 )

• frequently observed in mice

increased oxygen consumption ( J:133127 )

• 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

abnormal glucose tolerance ( J:133127 )

• 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

increased urine antidiuretic hormone level ( J:160869 )

• urine vasopressin concentration is increased

decreased urine osmolality ( J:160869 )

• several 18-22 month old mice excrete large volumes of urine with low osmolarity

limbs/digits/tail

abnormal digit development ( J:81010 )

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

digestive/alimentary system

exocrine pancreas atrophy ( J:81010 )

• the pancreas shows patchy atrophy of the exocrine epithelium

cardiovascular system

heart right ventricle hypertrophy ( J:81010 )

• occurs as a result of lung inflammation

immune system

decreased CD8-positive, alpha-beta T cell number ( J:81010 )

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

increased immunoglobulin level ( J:160869 )

• sinusoids of the liver show deposits

increased anti-nuclear antigen antibody level ( J:160869 )

• 73% of mice have anti-nuclear antibodies

glomerulonephritis ( J:160869 )

• immunoglobulin deposits in the kidney

lung inflammation ( J:81010 )

• lungs are infiltrated with neutrophils suggesting chronic pulmonary infection

interstitial pneumonia ( J:81010 )

• occurs consistently in mice

hematopoietic system

decreased CD8-positive, alpha-beta T cell number ( J:81010 )

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

increased immunoglobulin level ( J:160869 )

• sinusoids of the liver show deposits

adipose tissue

abnormal inguinal fat pad morphology ( J:133127 )

• 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

oligozoospermia ( J:81010 )

• there are 20-fold less mature sperm in the seminal fluid compared to wild-type littermates

teratozoospermia ( J:81010 )

• majority of sperm are abnormal with small, rounded cell bodies and blunted or absent hooks in the tail

abnormal sperm flagellum morphology ( J:81010 )

• many of the sperm have flagellas that are fine and lack associated cell bodies

globozoospermia ( J:81010 )

• many sperm retain cytoplasm around their nucleus

• majority of sperm are abnormal with small, rounded cell bodies

abnormal spermatid morphology ( J:81010 )

• 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

increased male germ cell apoptosis ( J:81010 )

• all mice have increased levels of spermatocyte apoptosis

immotile sperm ( J:81010 )

• virtually none of the mature sperm cells are motile

abnormal cellular respiration ( J:133127 )

• 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

decreased brain weight ( J:133127 )

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

renal/urinary system

increased urine antidiuretic hormone level ( J:160869 )

• urine vasopressin concentration is increased

decreased urine osmolality ( J:160869 )

• several 18-22 month old mice excrete large volumes of urine with low osmolarity

abnormal renal glomerulus morphology ( J:160869 )

• the glomeruli of 24 month old animals are hypercellular with evidence of reduced vascularity

glomerulonephritis ( J:160869 )

• immunoglobulin deposits in the kidney

renal glomerular immunoglobulin deposits ( J:160869 )

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

Allelic Composition	Actb^{tm3.1(Sirt1)Npa}/Actb⁺ Sirt1^tm1Mcby/Sirt1^tm1Mcby
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Actb^{tm3.1(Sirt1)Npa} mutation (1 available); any Actb mutation (53 available)
Sirt1^tm1Mcby mutation (2 available); any Sirt1 mutation (81 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

reproductive system

reproductive system phenotype ( J:160212 )

N	• unlike Sirt1^tm1Mcby homozygotes, mice are fertile

growth/size/body

growth/size/body region phenotype ( J:160212 )

N	• unlike Sirt1^tm1Mcby homozygotes, mice exhibit normal body size and weight

vision/eye

vision/eye phenotype ( J:160212 )

N	• unlike Sirt1^tm1Mcby homozygotes, eyelids open

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