Mouse Genome Informatics
hm
    Sirt1tm1Mcby/Sirt1tm1Mcby
involves: 129S1/Sv * 129X1/SvJ * CD-1
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
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

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

reproductive system
• all mice have increased levels of spermatocyte apoptosis
• 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
• 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
• 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
• virtually none of the mature sperm cells are motile

growth/size/body
• 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
• many of the sperm have flagellas that are fine and lack associated cell bodies
• all mice have increased levels of spermatocyte apoptosis
• 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
OMIM IDRef(s)
Diabetes Insipidus, Nephrogenic, Autosomal 125800 J:160869