Analysis Tools
nervous system
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• 1 female presented with primitive neuroendocrine tumor in the liver, pancreas, and thymus at 21 months of age
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mortality/aging
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• spontaneous deaths in 9 of 59 mice and increasing problems in well-being (including illness, weight loss, dental problems, visible tumors, and dermatitis) leading to euthanasia in 13 of 59 of mice at 18 months of age
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reproductive system
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• significantly reduced oocyte number in ovaries at P30
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• absence of female germ cells at 6 months of age
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• degeneration of male germ cells starting at P13
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• total absence of male germ cells at 1 month of age
• absence of female germ cells at 6 months of age
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• hilus cell hyperplasia in adult female mice
• ovarian lipid cell hyperplasia in some females at 6 months of age
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• ovarian Sertoli cell tumors in 14 of 204 females at 14-22 months of age
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ovary cyst
(
J:232482
)
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• ovarian cysts in some females at 6 months of age
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• progressive neutral fat accumulation in and around Leydig cells starting at 1 month of age, with excessive lipid accumulation evident at 18 months
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• Leydig cell hyperplasia starting at P13 and increasing with age
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• histological evidence of testicular (germ cell) degeneration as early as P13
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small gonad
(
J:232482
)
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• hypogonadism in >75 % of mice
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small testis
(
J:232482
)
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• testis size is ~30% of that in control mice at >6 months of age
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infertility
(
J:232482
)
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• both males and females are infertile
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• females are able to become pregnant at the age of 6 weeks but older females are infertile
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• males fail to reproduce at any age from postnatal week 6 onwards
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growth/size/body
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• enlarged pancreas in about one third of mice after 12 months of age
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ovary cyst
(
J:232482
)
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• ovarian cysts in some females at 6 months of age
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weight loss
(
J:232482
)
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• up to 20% weight loss in about one third of mice after 12 months of age
• males start losing weight at 6 months and females after 12 months of age
• however, early weight development is normal in both sexes
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• tendency towards enlarged relative liver size, with pronounced hepatomegaly in a subset of female mice at 22-24 months of age
• however, hepatomegaly is infrequent at 18 months of age and no evidence of hepatic peliosis is observed
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• splenomegaly in about one third of mice after 12 months of age
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craniofacial
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• sagittal skull width is 9.6 +/- 0.1 mm versus 9.8 +/- 0.1 mm in control mice
• coronal skull width 13.7 +/- 0.2 mm versus 14.0 +/- 0.2 mm in control mice
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• significantly smaller than normal skull size at 6 months of age
• however, lengths of long bones (humeri, ulnae and femurs) are normal
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endocrine/exocrine glands
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• enlargement of pancreas with a granular appearance in about one third of mice after 12 months of age
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• enlarged pancreas in about one third of mice after 12 months of age
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• hilus cell hyperplasia in adult female mice
• ovarian lipid cell hyperplasia in some females at 6 months of age
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• ovarian Sertoli cell tumors in 14 of 204 females at 14-22 months of age
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ovary cyst
(
J:232482
)
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• ovarian cysts in some females at 6 months of age
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• progressive neutral fat accumulation in and around Leydig cells starting at 1 month of age, with excessive lipid accumulation evident at 18 months
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• Leydig cell hyperplasia starting at P13 and increasing with age
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small testis
(
J:232482
)
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• testis size is ~30% of that in control mice at >6 months of age
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• histological evidence of testicular (germ cell) degeneration as early as P13
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cardiovascular system
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• sinusoidal dilatation at 22-24 months of age
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• at 6 months of age, most mice exhibit more trabeculated ventricular walls relative to wild-type controls
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• H&E staining of heart sections revealed myocardial hypertrabeculation at 6 months of age
• endothelial (anti-CD34) immunostaining) detected in trabeculations of the ventricular wall indicates non-compaction cardiomyopathy
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liver/biliary system
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• H&E staining of liver sections at 1-, 4-, 6- and 18 months of age shows progressive vacuolization of the liver
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• sinusoidal dilatation at 22-24 months of age
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• tendency towards enlarged relative liver size, with pronounced hepatomegaly in a subset of female mice at 22-24 months of age
• however, hepatomegaly is infrequent at 18 months of age and no evidence of hepatic peliosis is observed
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• neutral lipid accumulation in liver (mostly triacylglycerols) starting at ~4-6 months of age, with both staining intensity and lipid droplet size increasing with age
• lipid accumulation in liver is highly variable and more prominent in females than in males
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• fatty liver in about one third of mice after 12 months of age
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homeostasis/metabolism
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• after 24-h fasting, adult (6-month-old) male mice show increased fasting blood glucose levels
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• increased FSH levels in male mice at 4 months of age
• however, testosterone levels remain normal
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• increased LH levels in male mice at 4 months of age
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• after 24-h fasting, adult (6-month-old) male mice display low fasting serum insulin levels
• however, number, size and distribution of pancreatic beta-islets is normal
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• reduced respiratory exchange ratio (RER) in 20-month-old mice fed a fat-enriched Western diet since weaning
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• neutral lipid accumulation in liver (mostly triacylglycerols) starting at ~4-6 months of age, with both staining intensity and lipid droplet size increasing with age
• lipid accumulation in liver is highly variable and more prominent in females than in males
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immune system
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• splenomegaly in about one third of mice after 12 months of age
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neoplasm
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• primitive neuroendocrine tumors, lymphomas, and neuroendocrine carcinomas only occasionally seen
• 2 of 204 mice (females) presented with multiple tumors of the same type in different locations of the body
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• ovarian Sertoli cell tumors in 14 of 204 females at 14-22 months of age
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• 1 female presented with lymphoma in the lymph nodes, ovaries, and thymus, with distinct tumors in the area of the abdomen at 15 months of age
• 1 male presented with lymphoma in the lymph nodes at 18 months of age
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• 1 female presented with primitive neuroendocrine tumor in the liver, pancreas, and thymus at 21 months of age
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• 1 female presented with neuroendocrine carcinoma of the thymus at 14 months of age
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hematopoietic system
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• splenomegaly in about one third of mice after 12 months of age
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behavior/neurological
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• reduced water consumption in 20-month-old mice fed a fat-enriched Western diet since weaning
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• reduced food intake in 20-month-old male mice fed a fat-enriched Western diet since weaning
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• reduced mobility in about one third of mice after 12 months of age
• lower physical activity in 20-month-old mice fed a fat-enriched Western diet since weaning
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muscle
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• at 6 months of age, most mice exhibit more trabeculated ventricular walls relative to wild-type controls
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• H&E staining of heart sections revealed myocardial hypertrabeculation at 6 months of age
• endothelial (anti-CD34) immunostaining) detected in trabeculations of the ventricular wall indicates non-compaction cardiomyopathy
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skeleton
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• sagittal skull width is 9.6 +/- 0.1 mm versus 9.8 +/- 0.1 mm in control mice
• coronal skull width 13.7 +/- 0.2 mm versus 14.0 +/- 0.2 mm in control mice
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• significantly smaller than normal skull size at 6 months of age
• however, lengths of long bones (humeri, ulnae and femurs) are normal
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cellular
| N |
• normal number, structure and distribution of liver peroxisomes relative to control mice
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• significantly reduced oocyte number in ovaries at P30
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• absence of female germ cells at 6 months of age
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• degeneration of male germ cells starting at P13
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• total absence of male germ cells at 1 month of age
• absence of female germ cells at 6 months of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| mulibrey nanism | DOID:0050436 |
OMIM:253250 |
J:232482 | |
