Mouse Genome Informatics
cn
    Snord116tm1Uta/Snord116+
Tg(Zp3-cre)93Knw/0

involves: C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
N
• almost all mutants with the paternally inherited deletion survive to adulthood and appear healthy at 18 months (J:131427)

growth/size
• when fed a high-fat diet for 4 months, mutants carrying the paternally-inherited deletion allele have significantly lower body fat than wild-type animals (mutant males -6.9%, mutant females -7.2% lower than wild-type)
• 5 month-old mutant males on regular chow diet show an insignificant trend (-3.6%) toward decreased body fat content while females show a significant decrease of 4.2% relative to wild-type; 9-month old animals on a regular chow diet significantly lower body fat content (-9% in mutant males, -5% in females)
• on high-fat and normal chow diets, animals carrying the paternally-inherited deletion allele display decreased fat storage compared to wild-type animals
• at 5 months of age, body lengths of mutant males and females are shorter by around 4 and 3%, respectively, than wild-type mice (differences are statistically significant)
• when fed a high-fat diet for 4 months from 8 weeks of age, mutants carrying the paternally-inherited deletion gain less weight than wild-type littermates, with the differences more pronounced in males
• at birth, pups with the paternally-inherited allele are indistinguishable from normal littermates, but beginning at P2, mutants fail to gain weight as effectively as littermates; by 3 weeks, mutant weights are 60% of wild-type male and female weights
• growth rates appear to normalize after weaning, but weight differences persist to maturity in both genders

behavior/neurological
N
• unlike other mouse models of Prader-Willi syndrome, mutant pups carrying the paternally-inherited deletion show normal milk intake, righting ability, and muscle tone and strenght after birth and during early postnatal period (J:131427)
• when provided with a high-fat diet, both wild-type and mutant animals reduce their total food intake, but both mutant males and females have lower food intake during the 'day-time' phase relative to wild-type animals (total energy intake is similar to wild-type, indicating that mutants compensate for reduced 'day-time' intake by increasing intake during dark-phase)
• at 6 months of age, both males and females carrying the paternally-inherited deletion allele show increases in daily food intake normalized to body weight (22% or 32%, respectively; at 3 months, males show significant hyperphagia relative to wild-type males, but to a lesser degree than at 6 months, while in females carrying the paternally-inherited deletion allele, daily food intake increases do not reach significance
• at 10 months, males and females carrying the paternally-inherited deletion allele display significant hyperphagia with daily food intake increased by 31 and 29% respectively compared to wild-type animals
• 3-4 month old mice with the paternally-inherited deletion exhibit increased anxiety-relatted behavior in elevated plus-maze tests (more entries into and time spent in closed arms of maze relative to wild-type mice)
• in accelerating rotarod trials at 2 and 5 months of age, mice carrying the paternally-inherited deletion display essentially flat learning curves (little improvement) over a 6-day training period, whereas control animals display significant improvements

nervous system
• at P5 and 13, brain weight is only slight decreased (95% and 92%, respectively, of wild-type brain weight)

reproductive system
N
• testis and ovary sizes of mutants carrying the paternally-inherited deletion are proportional to their body size, and histologically normal (J:131427)
• in mutant females with the paternally-inherited deletion, vaginal opening is delayed by 3.7 days

endocrine/exocrine glands
N
• morphology of pituitary gland in mutants is normal (J:131427)

homeostasis/metabolism
• when mice are restricted to 80% of their normal food intake levels, wild-type mice gradually lose weight but animals carrying the paternally-inherited deletion allele are better at maintaining their weight (females are significantly better, but males also show improved weight stability compared to wild-type)
• when fed a high-fat diet for 4 months from 8 weeks of age, mutants carrying the paternally-inherited deletion gain less weight than wild-type littermates, with the differences more pronounced in males
• on a high-fat diet, males carrying the paternally-inherited deletion allele have lower resting blood glucose levels and display a smaller peak level after glucose injecion compared to wild-type males
• when allowed ad libitum food access, adult mice carrying the paternally-inherited deletion allele have ghrelin levels 2.3-fold higher than in wild-type animals
• animals with paternally-inherited mutant allele have 39% of wild-type level at 4 weeks of age, and 57% of wild-type levels at 8 weeks
• mice carrying the paternally-inherited deletion allele have significantly rates of oxygen consumption
• mice carrying the paternally-inherited deletion allele exhibit a higher respiratory exchange ratio than wild-type mice
• on a normal diet, males carrying the paternally-inherited deletion have similar basal blood glucose levels to wild-type but display significantly increased response to insulin injection; mutant males fed a high-fat diet also display significantly increased insulin sensitivity

adipose tissue
• when fed a high-fat diet for 4 months, mutants carrying the paternally-inherited deletion allele have significantly lower body fat than wild-type animals (mutant males -6.9%, mutant females -7.2% lower than wild-type)
• 5 month-old mutant males on regular chow diet show an insignificant trend (-3.6%) toward decreased body fat content while females show a significant decrease of 4.2% relative to wild-type; 9-month old animals on a regular chow diet significantly lower body fat content (-9% in mutant males, -5% in females)
• on high-fat and normal chow diets, animals carrying the paternally-inherited deletion allele display decreased fat storage compared to wild-type animals

digestive/alimentary system
• stomachs in animals receiving paternally-inherited mutant allele are significantly smaller than in wild-type littermates; at P5 and 13, stomachs are 67 and 68% the size of wild-type

liver/biliary system
• size is strikingly reduced in size upon examination at P5 and 13
• at P5, liver weight is 72% of wild-type animals, and at p13, liver weight is only 56% of wild-type

cellular
• the Snord116 cluster is imprinted and the maternal copy is silenced during oogenesis; only inheritance of the paternal allele with the Snord116 cluster deletion produces the growth deficiency and polyphagia phenotypes in mice
• when offspring have maternal inheritance of the deleted allele, they are normal in size and show normal lifespans

Mouse Models of Human Disease
OMIM IDRef(s)
Prader-Willi Syndrome; PWS 176270 J:131427