Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129P2 via E14-1 ES cell line   Donating Investigator Paul Kelly,   Faculte de Medecine Necker

Appearance
black
Related Genotype: a/a

Description
There is complete female sterility due to abberant estrous cycles, abnormal preimplantation development of eggs, no implantation of blastocysts, lack of pseudopregnancy. Males show slightly delayed fertility. Mammary development is markedly affected. Homozygotes have no mammary development and do not lactate. Heterozygotes are unable to lactate after the first pregnancies, but attain some degree of lactation as they age or after multiple pregnancies. Serum prolactin levels are increased 60 - 100 fold in both males and females. Maternal behavior is diminished in pimiparous and nulliparous animals. Bone remodelling is decreased in homozygote mutants.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Prlr^tm1Cnp/Prlr⁺

        either: 129/Sv or (involves: 129P2/OlaHsd * C57BL/6)

• behavior/neurological phenotype
• abnormal maternal nurturing (MGI Ref ID J:38093)
  • some mothers scattered their pups, often burying them in sawdust
• abnormal pup retrieval (MGI Ref ID J:38093)
  • when the mother reformed the nest, a pup was often left outside and not retrieved, whereas the others were suckled
• endocrine/exocrine gland phenotype
• abnormal lactation (MGI Ref ID J:38093)
  • failure of lactation attributable after first, but not subsequent, pregancies
• abnormal mammary gland development (MGI Ref ID J:38093)
  • impaired development after first, but not subsequent, pregnancies
• reproductive system phenotype
• abnormal lactation (MGI Ref ID J:38093)
  • failure of lactation attributable after first, but not subsequent, pregancies
• abnormal mammary gland development (MGI Ref ID J:38093)
  • impaired development after first, but not subsequent, pregnancies

Prlr^tm1Cnp/Prlr⁺

        Background Not Specified

• behavior/neurological phenotype
• abnormal pup retrieval (MGI Ref ID J:83247)
  • primiparous females did not retrieve foster pups as wild-type mice did
• skin/coat/nails phenotype
• abnormal hair cycle (MGI Ref ID J:70207)
  • intermediate timing of molting relative to homozygotes and wild-type mice

Prlr^tm1Cnp/Prlr^tm1Cnp

        either: 129/Sv or (involves: 129P2/OlaHsd * C57BL/6)

• behavior/neurological phenotype
• abnormal sexual interaction (MGI Ref ID J:38093)
  • females showed increased mating frequency
• endocrine/exocrine gland phenotype
• abnormal ovarian follicle number (MGI Ref ID J:38093)
  • reduced number of primary follicles
• reproductive system phenotype
• abnormal oogenesis (MGI Ref ID J:38093)
  • immature oocytes were released from the ovary
• abnormal ovarian follicle number (MGI Ref ID J:38093)
  • reduced number of primary follicles
• abnormal reproductive system physiology (MGI Ref ID J:38093)
  • fertilization was impaired
  • defective pre-implantation embryonic development
  • mating did not induce pseudopregnancy
• abnormal oviduct environment (MGI Ref ID J:38093)
• abnormal ovulation (MGI Ref ID J:38093)
  • fewer than normal eggs are ovulated
• abnormal uterine environment (MGI Ref ID J:38093)
• abnormal decidualization (MGI Ref ID J:38093)
  • the uterus was refractory to implantation, though occasional implanted blastocysts were observed
  • fertilized single and two-cell stage embryos were viable when reimplanted into pseudopregnant (C57BL/6 x CBA)F1 hosts
• female infertility (MGI Ref ID J:38093)
• male infertility (MGI Ref ID J:38093)
  • 3 of 15 males were infertile
• reduced male fertility (MGI Ref ID J:38093)
  • 5 of 15 males were showed impaired fertility

Prlr^tm1Cnp/Prlr^tm1Cnp

        Background Not Specified

• skin/coat/nails phenotype
• abnormal hair cycle (MGI Ref ID J:70207)
  • earlier molting in both males and females
  • exacerbated in females, eliminating sexual dimorphism associated with murine hair replacement

View Research Applications

Research Applications

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

Prlr^tm1Cnp related

Cancer Research
Growth Factors/Receptors/Cytokines

Developmental Biology Research
Skeletal Defects

Endocrine Deficiency Research
Bone/Bone Marrow Defects
Mammary Gland Defects
Pancreas Defects

Neurobiology Research
Behavioral and Learning Defects

Reproductive Biology Research
Endocrine Deficiencies Affecting Gonads
Fertility Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Prlrtm1Cnp
Allele Name		targeted mutation 1, Paul A Kelly
Allele Type		Targeted (knock-out)
Common Name(s)		PRLRko; Prlr-;
Mutation Made By		Paul Kelly,   Faculte de Medecine Necker
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14.1
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Prlr, prolactin receptor
Chromosome		15
Gene Common Name(s)		AI987712; MGC105486; Pr-1; Pr-3; Prlr-rs1; RATPRLR; expressed sequence AI987712; hPRLrI; prolactin receptor 1; prolactin receptor 3; prolactin receptor related sequence 1;
Molecular Note		A neomycin cassette was inserted into the exon 5, creating an in-frame stop codon. Northern, Western, and binding data all demonstrate the lack of a functional receptor in homozygous mutant animals. [MGI Ref ID J:38093]

Genotyping

Genotyping Information

Genotyping Protocols

Prlr^tm1Cnp, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Ormandy CJ; Camus A; Barra J; Damotte D; Lucas B; Buteau H; Edery M; Brousse N; Babinet C; Binart N; Kelly PA. 1997. Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse. Genes Dev 11(2):167-78. [PubMed: 9009200]  [MGI Ref ID J:38093]

Additional References

Prlr^tm1Cnp related

Allan GJ; Tonner E; Barber MC; Travers MT; Shand JH; Vernon RG; Kelly PA; Binart N; Flint DJ. 2002. Growth hormone, acting in part through the insulin-like growth factor axis, rescues developmental, but not metabolic, activity in the mammary gland of mice expressing a single allele of the prolactin receptor. Endocrinology 143(11):4310-9. [PubMed: 12399427]  [MGI Ref ID J:80470]

Baran N; Kelly PA; Binart N. 2002. Characterization of a prolactin-regulated gene in reproductive tissues usingthe prolactin receptor knockout mouse model. Biol Reprod 66(4):1210-8. [PubMed: 11906943]  [MGI Ref ID J:75701]

Binart N; Helloco C; Ormandy CJ; Barra J; Clement-Lacroix P; Baran N; Kelly PA. 2000. Rescue of preimplantatory egg development and embryo implantation in prolactin receptor-deficient mice after progesterone administration. Endocrinology 141(7):2691-7. [PubMed: 10875275]  [MGI Ref ID J:115329]

Binart N; Imbert-Bollore P; Baran N; Viglietta C; Kelly PA. 2003. A short form of the prolactin (PRL) receptor is able to rescue mammopoiesis in heterozygous PRL receptor mice. Mol Endocrinol 17(6):1066-74. [PubMed: 12624115]  [MGI Ref ID J:83628]

Binart N; Melaine N; Pineau C; Kercret H; Touzalin AM; Imbert-Bollore P; Kelly PA; Jegou B. 2003. Male reproductive function is not affected in prolactin receptor-deficient mice. Endocrinology 144(9):3779-82. [PubMed: 12933648]  [MGI Ref ID J:85593]

Bouchard B; Ormandy CJ; Di Santo JP; Kelly PA. 1999. Immune system development and function in prolactin receptor-deficient mice. J Immunol 163(2):576-82. [PubMed: 10395643]  [MGI Ref ID J:56163]

Brisken C; Kaur S; Chavarria TE; Binart N; Sutherland RL; Weinberg RA; Kelly PA; Ormandy CJ. 1999. Prolactin controls mammary gland development via direct and indirect mechanisms. Dev Biol 210(1):96-106. [PubMed: 10364430]  [MGI Ref ID J:55578]

Clement-Lacroix P; Ormandy C; Lepescheux L; Ammann P; Damotte D; Goffin V; Bouchard B; Amling M; Gaillard-Kelly M; Binart N; Baron R; Kelly PA. 1999. Osteoblasts are a new target for prolactin: analysis of bone formation in prolactin receptor knockout mice. Endocrinology 140(1):96-105. [PubMed: 9886812]  [MGI Ref ID J:52026]

Craven AJ; Nixon AJ; Ashby MG; Ormandy CJ; Blazek K; Wilkins RJ; Pearson AJ. 2006. Prolactin delays hair regrowth in mice. J Endocrinol 191(2):415-25. [PubMed: 17088411]  [MGI Ref ID J:114701]

Craven AJ; Ormandy CJ; Robertson FG; Wilkins RJ; Kelly PA; Nixon AJ; Pearson AJ. 2001. Prolactin signaling influences the timing mechanism of the hair follicle: analysis of hair growth cycles in prolactin receptor knockout mice. Endocrinology 142(6):2533-9. [PubMed: 11356702]  [MGI Ref ID J:70207]

Fleenor D; Oden J; Kelly PA; Mohan S; Alliouachene S; Pende M; Wentz S; Kerr J; Freemark M. 2005. Roles of the lactogens and somatogens in perinatal and postnatal metabolism and growth: studies of a novel mouse model combining lactogen resistance and growth hormone deficiency. Endocrinology 146(1):103-12. [PubMed: 15388648]  [MGI Ref ID J:95779]

Flint DJ; Binart N; Boumard S; Kopchick JJ; Kelly P. 2006. Developmental aspects of adipose tissue in GH receptor and prolactin receptor gene disrupted mice: site-specific effects upon proliferation, differentiation and hormone sensitivity. J Endocrinol 191(1):101-11. [PubMed: 17065393]  [MGI Ref ID J:114956]

Freemark M; Avril I; Fleenor D; Driscoll P; Petro A; Opara E; Kendall W; Oden J; Bridges S; Binart N; Breant B; Kelly PA. 2002. Targeted deletion of the PRL receptor: effects on islet development, insulin production, and glucose tolerance. Endocrinology 143(4):1378-85. [PubMed: 11897695]  [MGI Ref ID J:106829]

Freemark M; Fleenor D; Driscoll P; Binart N; Kelly P. 2001. Body weight and fat deposition in prolactin receptor-deficient mice. Endocrinology 142(2):532-7. [PubMed: 11159821]  [MGI Ref ID J:67354]

Gallego MI; Binart N; Robinson GW; Okagaki R; Coschigano KT; Perry J; Kopchick JJ; Oka T; Kelly PA; Hennighausen L. 2001. Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects. Dev Biol 229(1):163-75. [PubMed: 11133161]  [MGI Ref ID J:66900]

Grimm SL; Seagroves TN; Kabotyanski EB; Hovey RC; Vonderhaar BK; Lydon JP; Miyoshi K; Hennighausen L; Ormandy CJ; Lee AV; Stull MA; Wood TL; Rosen JM. 2002. Disruption of steroid and prolactin receptor patterning in the mammary gland correlates with a block in lobuloalveolar development. Mol Endocrinol 16(12):2675-91. [PubMed: 12456789]  [MGI Ref ID J:125450]

Grosdemouge I; Bachelot A; Lucas A; Baran N; Kelly PA; Binart N. 2003. Effects of deletion of the prolactin receptor on ovarian gene expression. Reprod Biol Endocrinol 1:12. [PubMed: 12646063]  [MGI Ref ID J:102442]

Halperin J; Devi SY; Elizur S; Stocco C; Shehu A; Rebourcet D; Unterman TG; Leslie ND; Le J; Binart N; Gibori G. 2008. Prolactin Signaling through the Short Form of Its Receptor Represses Forkhead Transcription Factor FOXO3 and Its Target Gene Galt Causing a Severe Ovarian Defect. Mol Endocrinol 22(2):513-22. [PubMed: 17975019]  [MGI Ref ID J:130265]

Harris J; Stanford PM; Sutherland K; Oakes SR; Naylor MJ; Robertson FG; Blazek KD; Kazlauskas M; Hilton HN; Wittlin S; Alexander WS; Lindeman GJ; Visvader JE; Ormandy CJ. 2006. Socs2 and elf5 mediate prolactin-induced mammary gland development. Mol Endocrinol 20(5):1177-87. [PubMed: 16469767]  [MGI Ref ID J:108377]

Hilton HN; Stanford PM; Harris J; Oakes SR; Kaplan W; Daly RJ; Ormandy CJ. 2008. KIBRA interacts with discoidin domain receptor 1 to modulate collagen-induced signalling. Biochim Biophys Acta 1783(3):383-93. [PubMed: 18190796]  [MGI Ref ID J:133423]

Kedzia C; Lacroix L; Ameur N; Ragot T; Kelly PA; Caillou B; Binart N. 2005. Medullary thyroid carcinoma arises in the absence of prolactin signaling. Cancer Res 65(18):8497-503. [PubMed: 16166330]  [MGI Ref ID J:101609]

Le Provost F; Miyoshi K; Vilotte JL; Bierie B; Robinson GW; Hennighausen L. 2005. SOCS3 promotes apoptosis of mammary differentiated cells. Biochem Biophys Res Commun 338(4):1696-701. [PubMed: 16289036]  [MGI Ref ID J:104012]

Lindeman GJ; Wittlin S; Lada H; Naylor MJ; Santamaria M; Zhang JG; Starr R; Hilton DJ; Alexander WS; Ormandy CJ; Visvader J. 2001. SOCS1 deficiency results in accelerated mammary gland development and rescues lactation in prolactin receptor-deficient mice. Genes Dev 15(13):1631-6. [PubMed: 11445538]  [MGI Ref ID J:70408]

Long W; Wagner KU; Lloyd KC; Binart N; Shillingford JM; Hennighausen L; Jones FE. 2003. Impaired differentiation and lactational failure of Erbb4-deficient mammary glands identify ERBB4 as an obligate mediator of STAT5. Development 130(21):5257-68. [PubMed: 12954715]  [MGI Ref ID J:86319]

Lucas BK; Ormandy CJ; Binart N; Bridges RS; Kelly PA. 1998. Null mutation of the prolactin receptor gene produces a defect in maternal behavior. Endocrinology 139(10):4102-7. [PubMed: 9751488]  [MGI Ref ID J:83247]

Mak GK; Enwere EK; Gregg C; Pakarainen T; Poutanen M; Huhtaniemi I; Weiss S. 2007. Male pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior. Nat Neurosci 10(8):1003-11. [PubMed: 17603480]  [MGI Ref ID J:124216]

McClellan KA; Robertson FG; Kindblom J; Wennbo H; Tornell J; Bouchard B; Kelly PA; Ormandy CJ. 2001. Investigation of the role of prolactin in the development and function of the lacrimal and harderian glands using genetically modified mice Invest Ophthalmol Vis Sci 42(1):23-30. [PubMed: 11133844]  [MGI Ref ID J:66544]

Nilsson L; Binart N; Bohlooly-Y M; Bramnert M; Egecioglu E; Kindblom J; Kelly PA; Kopchick JJ; Ormandy CJ; Ling C; Billig H. 2005. Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue. Biochem Biophys Res Commun 331(4):1120-6. [PubMed: 15882993]  [MGI Ref ID J:98282]

Oakes SR; Robertson FG; Kench JG; Gardiner-Garden M; Wand MP; Green JE; Ormandy CJ. 2007. Loss of mammary epithelial prolactin receptor delays tumor formation by reducing cell proliferation in low-grade preinvasive lesions. Oncogene 26(4):543-53. [PubMed: 16862169]  [MGI Ref ID J:117839]

Reese J; Binart N; Brown N; Ma WG; Paria BC; Das SK; Kelly PA; Dey SK. 2000. Implantation and decidualization defects in prolactin receptor (PRLR)-deficient mice are mediated by ovarian but not uterine PRLR. Endocrinology 141(5):1872-81. [PubMed: 10803598]  [MGI Ref ID J:61911]

Riedlinger G; Okagaki R; Wagner KU; Rucker EB rd; Oka T; Miyoshi K; Flaws JA; Hennighausen L. 2002. Bcl-x is not required for maintenance of follicles and corpus luteum in the postnatal mouse ovary. Biol Reprod 66(2):438-44. [PubMed: 11804960]  [MGI Ref ID J:108582]

Robertson FG; Harris J; Naylor MJ; Oakes SR; Kindblom J; Dillner K; Wennbo H; Tornell J; Kelly PA; Green J; Ormandy CJ. 2003. Prostate development and carcinogenesis in prolactin receptor knockout mice. Endocrinology 144(7):3196-205. [PubMed: 12810576]  [MGI Ref ID J:84352]

Schuff KG; Hentges ST; Kelly MA; Binart N; Kelly PA; Iuvone PM; Asa SL; Low MJ. 2002. Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms. J Clin Invest 110(7):973-81. [PubMed: 12370275]  [MGI Ref ID J:79683]

Shingo T; Gregg C; Enwere E; Fujikawa H; Hassam R; Geary C; Cross JC; Weiss S. 2003. Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin. Science 299(5603):117-20. [PubMed: 12511652]  [MGI Ref ID J:83248]

Viengchareun S; Servel N; Feve B; Freemark M; Lombes M; Binart N. 2008. Prolactin Receptor Signaling Is Essential for Perinatal Brown Adipocyte Function: A Role for Insulin-like Growth Factor-2. PLoS ONE 3(2):e1535. [PubMed: 18253483]  [MGI Ref ID J:132155]

Zhou J; Chehab R; Tkalcevic J; Naylor MJ; Harris J; Wilson TJ; Tsao S; Tellis I; Zavarsek S; Xu D; Lapinskas EJ; Visvader J; Lindeman GJ; Thomas R; Ormandy CJ; Hertzog PJ; Kola I; Pritchard MA. 2005. Elf5 is essential for early embryogenesis and mammary gland development during pregnancy and lactation. EMBO J 24(3):635-44. [PubMed: 15650748]  [MGI Ref ID J:96237]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.