Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.Cg(129S2)-Prltm1Hmn/J    (Changed: 15-DEC-04 ) B6.Cg-Prltm1Hmn/J    (Changed: 15-DEC-04 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N9 Generation Definitions   Donating Investigator Nelson D. Horseman,   University of Cincinnati

Description
Mice that are homozygous for the null Prl allele are viable, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous null females have an irregular estrous cycle and are completely infertile. Homozygous null males and heterozygous females exhibit no fertility problems. The targeted insertion of a neomycin resistance gene into exon 4 results in a truncated Prl transcript that produces an 11 kDa prolactin protein that lacks any detectable bioactivity. Mammary gland development is marked by an absence of terminal or lateral lobulation. The disruption of the prolactin gene appears to have no effects on the hematopoietic system.

Development
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter and a herpes simplex virus thymidine kinase was used to disrupt Prl exon 4 which encodes the second alpha helix of the prolactin protein. The construct was transfected into D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and chimeric animals generated.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Prl^tm1Hmn/Prl^tm1Hmn

        involves: 129S2/SvPas

• endocrine/exocrine gland phenotype
• *normal* endocrine/exocrine gland phenotype
  • surprisingly, male homozygotes show normal plasma testosterone levels despite reduced LH levels   (MGI Ref ID J:83246)
  • in vitro, both basal and LH-stimulated testosterone release remains unaffected   (MGI Ref ID J:83246)
• • abnormal mammary gland morphology
    • at 6 weeks of age, mutant mammary glands show only some mild signs of hyperplasia and neutrophil infiltration   (MGI Ref ID J:45243)
  • • abnormal mammary gland development
      • female homozygotes display impaired pre-lactogenic mammary gland development   (MGI Ref ID J:45243)
    • • abnormal branching of the mammary ductal tree
        • in adult virgin female homozygotes, the ductal system comprises an extended branching network but is devoid of terminal and lateral lobulation   (MGI Ref ID J:45243)
        • at 5 months of age, mutant mammary ducts terminate as tapered tubes, blunt-ending tubes, or terminal end buds   (MGI Ref ID J:45243)
        • however, no increase in the number of branches is observed during mammary development   (MGI Ref ID J:45243)
  • abnormal pituitary gland morphology
    • at 6-8 weeks of age, female homozygotes display hypertrophic pituitaries with abnormal cell boundaries   (MGI Ref ID J:79661)
    • many cells have increased cytoplasmic volumes with granular accumulations of an N-terminal peptide encoded by the disrupted gene   (MGI Ref ID J:79661)
  • • abnormal gonadotroph morphology
      • 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   (MGI Ref ID J:79661)
    • decreased lactotroph cell number
      • at 6 weeks of age, homozygotes show a slight decrease in the volume of acidophilic cells in the anterior pituitary gland   (MGI Ref ID J:45243)
    • enlarged pituitary gland
      • male homozygotes display strikingly enlarged pituitary glands   (MGI Ref ID J:83246)
      • at 15-18 months of age, all aged female homozygotes show obviously enlarged pituitaries, consistent with the development of adenomas and vascular congestion   (MGI Ref ID J:79661)
    • • increased pituitary gland weight
        • in male homozygotes, pituitary weight is increased by ~100% relative to that in wild-type males   (MGI Ref ID J:83246)
      • pituitary gland hyperplasia
        • at 6 weeks of age, female homozygotes display pituitary hyperplasia   (MGI Ref ID J:79661)
  • abnormal pituitary secretion
    • 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   (MGI Ref ID J:83246)
  • decreased seminal vesicle weight
    • 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)   (MGI Ref ID J:83246)
    • however, no significant differences in body weight or in the weights of testes or epididymides are observed   (MGI Ref ID J:83246)
  • small prostate gland ventral lobe
    • 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)   (MGI Ref ID J:83246)
    • however, no significant differences in the weights of coagulating glands are observed   (MGI Ref ID J:83246)
• homeostasis/metabolism phenotype
• decreased circulating estrogen level
  • 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)   (MGI Ref ID J:79661)
• • decreased circulating estradiol level
    • 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)   (MGI Ref ID J:79661)
• decreased dopamine level
  • dopamine levels in the median eminence are significantly reduced relative to those in wild-type controls   (MGI Ref ID J:83246)
  • however, dopamine content in the medial basal hypothalamus and anterior hypothalamus remains normal   (MGI Ref ID J:83246)
  • no significant differences in hypothalamic norepinephrine levels are observed in these regions   (MGI Ref ID J:83246)
• decreased follicle stimulating hormone level
  • 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   (MGI Ref ID J:83246)
• decreased luteinizing hormone level
  • 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   (MGI Ref ID J:83246)
• • decreased circulating luteinizing hormone level
    • 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)   (MGI Ref ID J:83246)
    • in contrast, plasma testosterone levels remain unaffected in mutant males   (MGI Ref ID J:83246)
• decreased prolactin level
  • at the time of death, no prolactin is detectable in mutant pituitary homogenates   (MGI Ref ID J:83246)
  • no prolactin is detectable in incubation medium with pituitaries from male mutants   (MGI Ref ID J:83246)
  • no prolactin bioactivity is detected in mutant pituitary extracts   (MGI Ref ID J:45243)
• • decreased circulating prolactin level   (MGI Ref ID J:45243)
• reproductive system phenotype
• abnormal estrous cycle
  • female homozygotes display highly irregular estrous cycles with multiple days of proestus and/or multiple days of estrus   (MGI Ref ID J:45243)
  • no consistent pattern of cycling is established in individual mutant females   (MGI Ref ID J:45243)
• • prolonged estrous cycle
    • mutant estous cycles can be longer than the normal 4-5 day cycle   (MGI Ref ID J:45243)
  • prolonged estrus
    • unlike wild-type females, which have only a single estrus day in each cycle, mutant females can have cycles with multiple days of estrus   (MGI Ref ID J:45243)
  • prolonged proestrus
    • unlike wild-type females, which have only a single proestrus day in each cycle, mutant females can have cycles with multiple days of proestrus   (MGI Ref ID J:45243)
  • short estrous cycle
    • mutant estous cycles can be shorter than the normal 4-5 day cycle   (MGI Ref ID J:45243)
• decreased seminal vesicle weight
  • 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)   (MGI Ref ID J:83246)
  • however, no significant differences in body weight or in the weights of testes or epididymides are observed   (MGI Ref ID J:83246)
• failure of embryo implantation
  • female homozygotes ovulate normal numbers of eggs which can be fertilized but fail to progress to implantation   (MGI Ref ID J:45243)
• female infertility
  • female homozygotes are completely infertile due to an implantation defect   (MGI Ref ID J:45243)
  • in contrast, male homozygotes are fully fertile and produce normal litter sizes   (MGI Ref ID J:45243)
• small prostate gland ventral lobe
  • 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)   (MGI Ref ID J:83246)
  • however, no significant differences in the weights of coagulating glands are observed   (MGI Ref ID J:83246)
• embryogenesis phenotype
• failure of embryo implantation
  • female homozygotes ovulate normal numbers of eggs which can be fertilized but fail to progress to implantation   (MGI Ref ID J:45243)
• nervous system phenotype
• abnormal pituitary gland morphology
  • at 6-8 weeks of age, female homozygotes display hypertrophic pituitaries with abnormal cell boundaries   (MGI Ref ID J:79661)
  • many cells have increased cytoplasmic volumes with granular accumulations of an N-terminal peptide encoded by the disrupted gene   (MGI Ref ID J:79661)
• • abnormal gonadotroph morphology
    • 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   (MGI Ref ID J:79661)
  • decreased lactotroph cell number
    • at 6 weeks of age, homozygotes show a slight decrease in the volume of acidophilic cells in the anterior pituitary gland   (MGI Ref ID J:45243)
  • enlarged pituitary gland
    • male homozygotes display strikingly enlarged pituitary glands   (MGI Ref ID J:83246)
    • at 15-18 months of age, all aged female homozygotes show obviously enlarged pituitaries, consistent with the development of adenomas and vascular congestion   (MGI Ref ID J:79661)
  • • increased pituitary gland weight
      • in male homozygotes, pituitary weight is increased by ~100% relative to that in wild-type males   (MGI Ref ID J:83246)
    • pituitary gland hyperplasia
      • at 6 weeks of age, female homozygotes display pituitary hyperplasia   (MGI Ref ID J:79661)
• abnormal pituitary secretion
  • 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   (MGI Ref ID J:83246)
• decreased dopamine level
  • dopamine levels in the median eminence are significantly reduced relative to those in wild-type controls   (MGI Ref ID J:83246)
  • however, dopamine content in the medial basal hypothalamus and anterior hypothalamus remains normal   (MGI Ref ID J:83246)
  • no significant differences in hypothalamic norepinephrine levels are observed in these regions   (MGI Ref ID J:83246)
• tumorigenesis
• increased pituitary adenoma incidence
  • 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   (MGI Ref ID J:79661)
  • pituitary tumors synthesize the truncated peptide, suggesting that the tumors arise from the lactotroph lineage   (MGI Ref ID J:79661)
  • 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   (MGI Ref ID J:79661)
  • growth and transformation of pseudolactotrophs appears to be accelerated in females compared with males   (MGI Ref ID J:79661)
  • 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   (MGI Ref ID J:79661)
  • no pathologies or lesions other than pituitary adenomas are observed   (MGI Ref ID J:79661)
• immune system phenotype
• *normal* immune system phenotype
  • homozygotes display normal bone marrow B lymphopoiesis and myelopoiesis relative to heterozygous control littermates   (MGI Ref ID J:45243)
  • no differences in thymus cellularity or frequency of thymocyte subpopulations are observed   (MGI Ref ID J:45243)
  • a normal frequency of B and T cells is observed in the spleen and lymph nodes   (MGI Ref ID J:45243)
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • at 8 weeks of age, nulliparous female homozygotes display normal spontaneous maternal behavior (pup retrieval and crouching) toward foster pups   (MGI Ref ID J:45243)
• liver/biliary system phenotype
• decreased liver weight
  • 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)   (MGI Ref ID J:83246)
  • however, no significant differences in the weights of the spleen or adrenals are observed   (MGI Ref ID J:83246)
• integument phenotype
• abnormal mammary gland morphology
  • at 6 weeks of age, mutant mammary glands show only some mild signs of hyperplasia and neutrophil infiltration   (MGI Ref ID J:45243)
• • abnormal mammary gland development
    • female homozygotes display impaired pre-lactogenic mammary gland development   (MGI Ref ID J:45243)
  • • abnormal branching of the mammary ductal tree
      • in adult virgin female homozygotes, the ductal system comprises an extended branching network but is devoid of terminal and lateral lobulation   (MGI Ref ID J:45243)
      • at 5 months of age, mutant mammary ducts terminate as tapered tubes, blunt-ending tubes, or terminal end buds   (MGI Ref ID J:45243)
      • however, no increase in the number of branches is observed during mammary development   (MGI Ref ID J:45243)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Prl^tm1Hmn related

Developmental Biology Research

Endocrine Deficiency Research
Mammary Gland Defects

Reproductive Biology Research
Developmental Defects Affecting Gonads
      females only
Fertility Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Prltm1Hmn
Allele Name		targeted mutation 1, Nelson D Horseman
Allele Type		Targeted (knock-out)
Common Name(s)		PRL-;
Mutation Made By		Nelson Horseman,   University of Cincinnati
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Prl, prolactin
Chromosome		13
Gene Common Name(s)		AV290867; PRLB; PRLSD1; Prl1a1; Prol; RATPRLSD1; RNPROL; expressed sequence AV290867;
Molecular Note		A PGK neomycin cassette was inserted into exon 4. This sequence encodes the second alpha helix of the protein. RT-PCR analysis confirmed a lack of wild-type transcript in homozygous mutant mice. Western blotting of pituitary gland extracts revealed the presence of a unique immunoreactive ~10-kDa truncated protein product in homozygous mutant mice. Disrupted prolactin synthesis was confirmed by biological assays. [MGI Ref ID J:45243]

Genotyping

Genotyping Information

Genotyping Protocols

Prl^tm1Hmn, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Horseman ND; Zhao W; Montecino-Rodriguez E; Tanaka M; Nakashima K ; Engle SJ ; Smith F ; Markoff E ; Dorshkind K. 1997. Defective mammopoiesis, but normal hematopoiesis, in mice with a targeted disruption of the prolactin gene. EMBO J 16(23):6926-35. [PubMed: 9384572]  [MGI Ref ID J:45243]

Additional References

Prl^tm1Hmn related

Bao L; Tessier C; Prigent-Tessier A; Li F; Buzzio OL; Callegari EA; Horseman ND; Gibori G. 2007. Decidual prolactin silences the expression of genes detrimental to pregnancy. Endocrinology 148(5):2326-34. [PubMed: 17255200]  [MGI Ref ID J:129612]

Chen CC; Stairs DB; Boxer RB; Belka GK; Horseman ND; Alvarez JV; Chodosh LA. 2012. Autocrine prolactin induced by the Pten-Akt pathway is required for lactation initiation and provides a direct link between the Akt and Stat5 pathways. Genes Dev 26(19):2154-68. [PubMed: 23028142]  [MGI Ref ID J:188260]

Cruz-Soto ME; Scheiber MD; Gregerson KA; Boivin GP; Horseman ND. 2002. Pituitary tumorigenesis in prolactin gene-disrupted mice. Endocrinology 143(11):4429-36. [PubMed: 12399440]  [MGI Ref ID J:79661]

Donangelo I; Melmed S. 2005. Pathophysiology of pituitary adenomas. J Endocrinol Invest 28(11 Suppl):100-5. [PubMed: 16625857]  [MGI Ref ID J:116408]

Foster MP; Jensen ER; Montecino-Rodriguez E; Leathers H; Horseman N; Dorshkind K. 2000. Humoral and cell-mediated immunity in mice with genetic deficiencies of prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormone. Clin Immunol 96(2):140-9. [PubMed: 10900161]  [MGI Ref ID J:63735]

Hou Z; Bailey JP; Vomachka AJ; Matsuda M; Lockefeer JA; Horseman ND. 2000. Glycosylation-dependent cell adhesion molecule 1 (GlyCAM 1) is induced by prolactin and suppressed by progesterone in mammary epithelium Endocrinology 141(11):4278-83. [PubMed: 11089563]  [MGI Ref ID J:65575]

LaPensee CR; Horseman ND; Tso P; Brandebourg TD; Hugo ER; Ben-Jonathan N. 2006. The prolactin-deficient mouse has an unaltered metabolic phenotype. Endocrinology 147(10):4638-45. [PubMed: 16809445]  [MGI Ref ID J:113661]

Matsuda M; Imaoka T; Vomachka AJ; Gudelsky GA; Hou Z; Mistry M; Bailey JP; Nieport KM; Walther DJ; Bader M; Horseman ND. 2004. Serotonin regulates mammary gland development via an autocrine-paracrine loop. Dev Cell 6(2):193-203. [PubMed: 14960274]  [MGI Ref ID J:90035]

Matsutani T; Samy TS; Rue LW 3rd; Bland KI; Chaudry IH. 2005. Transgenic prolactin-/- mice: effect of trauma-hemorrhage on splenocyte functions. Am J Physiol Cell Physiol 288(5):C1109-16. [PubMed: 15601751]  [MGI Ref ID J:101237]

Obal F Jr; Garcia-Garcia F; Kacsoh B; Taishi P; Bohnet S; Horseman ND; Krueger JM. 2005. Rapid eye movement sleep is reduced in prolactin-deficient mice. J Neurosci 25(44):10282-9. [PubMed: 16267236]  [MGI Ref ID J:102363]

Phelps CJ; Horseman ND. 2000. Prolactin gene disruption does not compromise differentiation of tuberoinfundibular dopaminergic neurons. Neuroendocrinology 72(1):2-10. [PubMed: 10940733]  [MGI Ref ID J:63947]

Steger RW; Chandrashekar V; Zhao W; Bartke A; Horseman ND. 1998. Neuroendocrine and reproductive functions in male mice with targeted disruption of the prolactin gene. Endocrinology 139(9):3691-5. [PubMed: 9724019]  [MGI Ref ID J:83246]

Vomachka AJ; Pratt SL; Lockefeer JA; Horseman ND. 2000. Prolactin gene-disruption arrests mammary gland development and retards T-antigen-induced tumor growth. Oncogene 19(8):1077-84. [PubMed: 10713693]  [MGI Ref ID J:61017]

Walker TL; Vukovic J; Koudijs MM; Blackmore DG; Mackay EW; Sykes AM; Overall RW; Hamlin AS; Bartlett PF. 2012. Prolactin stimulates precursor cells in the adult mouse hippocampus. PLoS One 7(9):e44371. [PubMed: 22973440]  [MGI Ref ID J:191762]

Health & husbandry

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Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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