Analysis Tools
endocrine/exocrine glands
| N |
• surprisingly, male homozygotes show normal plasma testosterone levels despite reduced LH levels
• in vitro, both basal and LH-stimulated testosterone release remains unaffected
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• at 6-8 weeks of age, female homozygotes display hypertrophic pituitaries with abnormal cell boundaries
• many cells have increased cytoplasmic volumes with granular accumulations of an N-terminal peptide encoded by the disrupted gene
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• although pituitary GH cells appear to be normal, they are largely absent in areas of hyperplasia at 3 months and severely displaced in adenomatous sections at 15 months of age
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• at 6 weeks of age, homozygotes show a slight decrease in the volume of acidophilic cells in the anterior pituitary gland
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• at 15-18 months of age, all aged female homozygotes show obviously enlarged pituitaries, consistent with the development of adenomas and vascular congestion
(J:79661)
• male homozygotes display strikingly enlarged pituitary glands
(J:83246)
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• in male homozygotes, pituitary weight is increased by ~100% relative to that in wild-type males
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• at 6 weeks of age, female homozygotes display pituitary hyperplasia
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• at 6-8 weeks of age, female homozygotes display hypertrophic pituitaries with abnormal cell boundaries
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• at 8 months of age or later, all aged female homozygotes display large hyperemic pituitary adenomas composed of monomorphic, weakly eosinophilic cells with large perinuclear cytoplasmic inclusions
• pituitary tumors synthesize the truncated peptide, suggesting that the tumors arise from the lactotroph lineage
• pituitary cells cultured from 8-month-old or older homozygotes grow as colonies in soft agar whereas those from 3-month-old mice remain as single cells, suggesting that anchorage-independent growth of tumor cells is acquired between 3 and 8 months of age
• growth and transformation of pseudolactotrophs appears to be accelerated in females compared with males
• treatment of 8-month-old female homozygotes with bromocriptin (a dopamine agonist) reduces mean pituitary weight by 66% and results in tumor regression and cell shrinkage, not observed in untreated or vehicle-treated homozygotes
• no pathologies or lesions other than pituitary adenomas are observed
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• at 6 weeks of age, mutant mammary glands show only some mild signs of hyperplasia and neutrophil infiltration
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• female homozygotes display impaired pre-lactogenic mammary gland development
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• in adult virgin female homozygotes, the ductal system comprises an extended branching network but is devoid of terminal and lateral lobulation
• at 5 months of age, mutant mammary ducts terminate as tapered tubes, blunt-ending tubes, or terminal end buds
• however, no increase in the number of branches is observed during mammary development
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• the weights of mutant ventral prostates are significantly reduced relative to those in wild-type mice (12.3 +/- 0.94 mg versus 17.1 +/- 3.14 mg, respectively)
• however, the weights of coagulating glands are normal
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• the weights of mutant seminal vesicles (full) are significantly reduced relative to those in wild-type mice (282 +/- 16 mg versus 322 +/- 32 mg, respectively)
• however, no significant differences in body weight or in the weights of testes or epididymides are observed
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• in vitro, mutant pituitaries release significantly less LH and FSH when calculated on a weight basis; however, no differences are observed when calculated on a per pituitary basis
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homeostasis/metabolism
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• at 4 months of age, female homozygotes display significantly lower serum estrogen levels than wild-type controls (41.2 pg/ml versus 73.1 pg/ml, respectively)
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• at 4 months of age, female homozygotes display significantly lower serum 17beta-estradiol levels than wild-type controls (0.15 nM versus 0.27 nM, respectively)
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• dopamine levels in the median eminence are significantly reduced relative to those in wild-type controls
• however, dopamine content in the medial basal hypothalamus and anterior hypothalamus remains normal
• no significant differences in hypothalamic norepinephrine levels are observed in these regions
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• at the time of death, the contents of FSH per mg pituitary are markedly reduced relative to those in wild-type mice; however, when FSH contents are expressed on a per pituitary basis, the difference is not statistically significant
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• at the time of death, the contents of LH per mg pituitary are markedly reduced relative to those in wild-type mice; however, when LH contents are expressed on a per pituitary basis, the difference is not statistically significant
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• male homozygotes show significantly lower plasma LH levels than wild-type males (1.17 +/- 0.19 ng/ml versus 1.75 +/- 0.24 ng/ml, respectively)
• in contrast, plasma testosterone levels remain unaffected in mutant males
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• no prolactin bioactivity is detected in mutant pituitary extracts
(J:45243)
• at the time of death, no prolactin is detectable in mutant pituitary homogenates
(J:83246)
• no prolactin is detectable in incubation medium with pituitaries from male mutants
(J:83246)
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reproductive system
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• the weights of mutant ventral prostates are significantly reduced relative to those in wild-type mice (12.3 +/- 0.94 mg versus 17.1 +/- 3.14 mg, respectively)
• however, the weights of coagulating glands are normal
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• the weights of mutant seminal vesicles (full) are significantly reduced relative to those in wild-type mice (282 +/- 16 mg versus 322 +/- 32 mg, respectively)
• however, no significant differences in body weight or in the weights of testes or epididymides are observed
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• female homozygotes display highly irregular estrous cycles with multiple days of proestus and/or multiple days of estrus
• no consistent pattern of cycling is established in individual mutant females
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• unlike wild-type females, which have only a single estrus day in each cycle, mutant females can have cycles with multiple days of estrus
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• unlike wild-type females, which have only a single proestrus day in each cycle, mutant females can have cycles with multiple days of proestrus
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• mutant estous cycles can be longer than the normal 4-5 day cycle
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• mutant estous cycles can be shorter than the normal 4-5 day cycle
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• female homozygotes ovulate normal numbers of eggs which can be fertilized but fail to progress to implantation
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• female homozygotes are completely infertile due to an implantation defect
• in contrast, male homozygotes are fully fertile and produce normal litter sizes
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nervous system
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• at 6-8 weeks of age, female homozygotes display hypertrophic pituitaries with abnormal cell boundaries
• many cells have increased cytoplasmic volumes with granular accumulations of an N-terminal peptide encoded by the disrupted gene
|
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• although pituitary GH cells appear to be normal, they are largely absent in areas of hyperplasia at 3 months and severely displaced in adenomatous sections at 15 months of age
|
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• at 6 weeks of age, homozygotes show a slight decrease in the volume of acidophilic cells in the anterior pituitary gland
|
|
• at 15-18 months of age, all aged female homozygotes show obviously enlarged pituitaries, consistent with the development of adenomas and vascular congestion
(J:79661)
• male homozygotes display strikingly enlarged pituitary glands
(J:83246)
|
|
|
• in male homozygotes, pituitary weight is increased by ~100% relative to that in wild-type males
|
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• at 6 weeks of age, female homozygotes display pituitary hyperplasia
|
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• at 6-8 weeks of age, female homozygotes display hypertrophic pituitaries with abnormal cell boundaries
|
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• at 8 months of age or later, all aged female homozygotes display large hyperemic pituitary adenomas composed of monomorphic, weakly eosinophilic cells with large perinuclear cytoplasmic inclusions
• pituitary tumors synthesize the truncated peptide, suggesting that the tumors arise from the lactotroph lineage
• pituitary cells cultured from 8-month-old or older homozygotes grow as colonies in soft agar whereas those from 3-month-old mice remain as single cells, suggesting that anchorage-independent growth of tumor cells is acquired between 3 and 8 months of age
• growth and transformation of pseudolactotrophs appears to be accelerated in females compared with males
• treatment of 8-month-old female homozygotes with bromocriptin (a dopamine agonist) reduces mean pituitary weight by 66% and results in tumor regression and cell shrinkage, not observed in untreated or vehicle-treated homozygotes
• no pathologies or lesions other than pituitary adenomas are observed
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• in vitro, mutant pituitaries release significantly less LH and FSH when calculated on a weight basis; however, no differences are observed when calculated on a per pituitary basis
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neoplasm
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• at 8 months of age or later, all aged female homozygotes display large hyperemic pituitary adenomas composed of monomorphic, weakly eosinophilic cells with large perinuclear cytoplasmic inclusions
• pituitary tumors synthesize the truncated peptide, suggesting that the tumors arise from the lactotroph lineage
• pituitary cells cultured from 8-month-old or older homozygotes grow as colonies in soft agar whereas those from 3-month-old mice remain as single cells, suggesting that anchorage-independent growth of tumor cells is acquired between 3 and 8 months of age
• growth and transformation of pseudolactotrophs appears to be accelerated in females compared with males
• treatment of 8-month-old female homozygotes with bromocriptin (a dopamine agonist) reduces mean pituitary weight by 66% and results in tumor regression and cell shrinkage, not observed in untreated or vehicle-treated homozygotes
• no pathologies or lesions other than pituitary adenomas are observed
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immune system
| N |
• homozygotes display normal bone marrow B lymphopoiesis and myelopoiesis relative to heterozygous control littermates
• no differences in thymus cellularity or frequency of thymocyte subpopulations are observed
• a normal frequency of B and T cells is observed in the spleen and lymph nodes
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behavior/neurological
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N |
• at 8 weeks of age, nulliparous female homozygotes display normal spontaneous maternal behavior (pup retrieval and crouching) toward foster pups
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liver/biliary system
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• the weight of mutant livers is significantly reduced relative to that in wild-type mice (1.51 +/- 0.044 g versus 1.72 +/- 0.085 g, respectively)
• however, no significant differences in the weights of the spleen or adrenals are observed
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integument
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• at 6 weeks of age, mutant mammary glands show only some mild signs of hyperplasia and neutrophil infiltration
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• female homozygotes display impaired pre-lactogenic mammary gland development
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• in adult virgin female homozygotes, the ductal system comprises an extended branching network but is devoid of terminal and lateral lobulation
• at 5 months of age, mutant mammary ducts terminate as tapered tubes, blunt-ending tubes, or terminal end buds
• however, no increase in the number of branches is observed during mammary development
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