Description

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N?+2F4p + N1 (09-NOV-05)   Donating Investigator T. Kumar,   University of Kansas

Description
Activin receptor IIA deficient mice are viable. Homozygous males are fertile, while homozygous females are infertile. Follicle-stimulating hormone levels are reduced in mutant mice. Some skeletal and facial abnormalities, including micrognathia, cleft palate and defects in Meckel's cartilage are observed. These defects are reminiscent of Pierre-Robin syndrome in humans. Severe defects occasionally result in the perinatal or in utero death of a small number of homozygous mutant embryos.

Development
A targeting vector deleted a 0.23 kb of the sequence of exon 1 of the ActRcII gene. It was replaced by a PGK-hprt cassette. The strain originated on a B6,129 background.

Control Information

	Control
	Wild-type from the colony
	100903 B6129PF2/J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Pierre Robin Syndrome - 5

5 Conditionally targeted allele(s)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Acvr2a^tm1Zuk/Acvr2a^tm1Zuk

        either: 129 or (involves: 129S7/SvEvBrd * C57BL/6)

• lethality-prenatal/perinatal
• neonatal lethality (MGI Ref ID J:23924)
  • 22% (mice exhibiting craniofacial defects) died within minutes of birth
• craniofacial phenotype
• abnormal craniofacial bone morphology (MGI Ref ID J:23924)
  • mice displaying facial abnormalities died within minutes of birth
• mandible hypoplasia (MGI Ref ID J:23924)
  • 22% of the mice displayed hypoplastic mandibles
  • some mice displayed defects in the mandibular cartilage
• absent incisors (MGI Ref ID J:23924)
  • secondary to the hypoplastic mandibles
• cleft palate (MGI Ref ID J:23924)
  • secondary to the hypoplastic mandibles
• endocrine/exocrine gland phenotype
• *normal* endocrine/exocrine gland phenotype (MGI Ref ID J:23924)
  • normal lutenizing hormone (LH) levels in male mice
• abnormal ovary morphology (MGI Ref ID J:23924)
• abnormal ovarian follicle morphology (MGI Ref ID J:23924)
  • follicular atresia observed
• absent corpus luteum (MGI Ref ID J:23924)
• abnormal seminiferous tubule morphology (MGI Ref ID J:23924)
  • reduction in tubule volume
• small testis (MGI Ref ID J:23924)
  • exhibited from 21 d of age through adulthoods
• homeostasis/metabolism phenotype
• suppressed circulating follicle stimulating hormone level (MGI Ref ID J:23924)
  • decrease FSH levels in both males and females
• reproductive system phenotype
• *normal* reproductive system phenotype (MGI Ref ID J:23924)
  • normal stages of spermatogenesis
• abnormal estrous cycle (MGI Ref ID J:23924)
• abnormal ovary morphology (MGI Ref ID J:23924)
• abnormal ovarian follicle morphology (MGI Ref ID J:23924)
  • follicular atresia observed
• absent corpus luteum (MGI Ref ID J:23924)
• abnormal seminiferous tubule morphology (MGI Ref ID J:23924)
  • reduction in tubule volume
• abnormal uterus morphology (MGI Ref ID J:23924)
  • thin uterus
• azoospermia (MGI Ref ID J:23924)
  • epididymis devoid of spermatozoa at 42 days of age
• delayed male fertility (MGI Ref ID J:23924)
  • average age of male fertility was 78 d, compared to 59 d in heterozygous littermates
  • putatively resulting from a decrease in the amount of spermatozoa
• female infertility (MGI Ref ID J:23924)
• small testis (MGI Ref ID J:23924)
  • exhibited from 21 d of age through adulthoods
• skeleton phenotype
• abnormal craniofacial bone morphology (MGI Ref ID J:23924)
  • mice displaying facial abnormalities died within minutes of birth
• mandible hypoplasia (MGI Ref ID J:23924)
  • 22% of the mice displayed hypoplastic mandibles
  • some mice displayed defects in the mandibular cartilage
• vision/eye phenotype
• abnormal eyelid morphology (MGI Ref ID J:23924)
  • 11% of the mice exhibited closed eyelids
• digestive/alimentary phenotype
• cleft palate (MGI Ref ID J:23924)
  • secondary to the hypoplastic mandibles

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

Acvr2a^tm1Zuk/Acvr2a^tm1Zuk

        Background Not Specified

• endocrine/exocrine gland phenotype
• abnormal Sertoli cell morphology (MGI Ref ID J:71932)
  • 30 to 39% decrease in the number of sertoli cells relative to wild-type
• decreased testis weight (MGI Ref ID J:71932)
  • 60% reduction in weight relative to wild-type
• reproductive system phenotype
• abnormal Sertoli cell morphology (MGI Ref ID J:71932)
  • 30 to 39% decrease in the number of sertoli cells relative to wild-type
• decreased male germ cell number (MGI Ref ID J:71932)
  • reductions in the number of spermatogonia and round spermatids
• decreased testis weight (MGI Ref ID J:71932)
  • 60% reduction in weight relative to wild-type

View Research Applications

Research Applications

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

Acvr2a^tm1Zuk related

Reproductive Biology Research
Endocrine Deficiencies Affecting Gonads
Fertility Defects (females only)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Acvr2atm1Zuk
Allele Name		targeted mutation 1, Martin M Matzuk
Allele Type		Targeted (knock-out)
Common Name(s)		Acvr2-; actRcIIm1;
Strain of Origin		129S7/SvEvBrd-Hprt1b-m2
ES Cell Line Name		AB2.1
ES Cell Line Strain		129S7/SvEvBrd-Hprt1
Gene Symbol and Name		Acvr2a, activin receptor IIA
Chromosome		2
Gene Common Name(s)		ACTRII; ACVR2; ActRIIa; Acvr2; rActR-II; tActRII;
Molecular Note		A PGK-hprt minigene replaced a genomic fragment containing the initiation codon and the sequences encoding the signal peptide. Northern blot analysis indicated that no transcript was detectable in liver of homozygous mice. [MGI Ref ID J:23924]

Genotyping

Genotyping Information

Genotyping Protocols

Human HPRT, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Matzuk MM; Kumar TR; Bradley A. 1995. Different phenotypes for mice deficient in either activins or activin receptor type II [see comments] Nature 374(6520):356-60. [PubMed: 7885474]  [MGI Ref ID J:23924]

Additional References

Matzuk MM; Kumar TR; Vassalli A; Bickenbach JR; Roop DR; Jaenisch R; Bradley A. 1995. Functional analysis of activins during mammalian development [see comments] Nature 374(6520):354-6. [PubMed: 7885473]  [MGI Ref ID J:23923]

Acvr2a^tm1Zuk related

Coerver KA; Woodruff TK; Finegold MJ; Mather J; Bradley A; Matzuk MM. 1996. Activin signaling through activin receptor type II causes the cachexia-like symptoms in inhibin-deficient mice. Mol Endocrinol 10(5):534-43. [PubMed: 8732684]  [MGI Ref ID J:112001]

Kumar TR; Agno J; Janovick JA; Conn PM; Matzuk MM. 2003. Regulation of FSHbeta and GnRH receptor gene expression in activin receptor II knockout male mice. Mol Cell Endocrinol 212(1-2):19-27. [PubMed: 14654247]  [MGI Ref ID J:87886]

Kumar TR; Varani S; Wreford NG; Telfer NM; de Kretser DM; Matzuk MM. 2001. Male reproductive phenotypes in double mutant mice lacking both FSHbeta and activin receptor IIA. Endocrinology 142(8):3512-8. [PubMed: 11459797]  [MGI Ref ID J:108808]

Li Q; Karam SM; Coerver KA; Matzuk MM; Gordon JI. 1998. Stimulation of activin receptor II signaling pathways inhibits differentiation of multiple gastric epithelial lineages. Mol Endocrinol 12(2):181-92. [PubMed: 9482661]  [MGI Ref ID J:110642]

Ma X; Reyna A; Mani SK; Matzuk MM; Kumar TR. 2005. Impaired male sexual behavior in activin receptor type II knockout mice. Biol Reprod 73(6):1182-90. [PubMed: 16093358]  [MGI Ref ID J:115447]

Naz RK; Rajesh C. 2005. Gene knockouts that cause female infertility: search for novel contraceptive targets Front Biosci 10:2447-2459. [PubMed: 15970507]  [MGI Ref ID J:103183]

Wreford NG; Rajendra Kumar T; Matzuk MM; de Kretser DM. 2001. Analysis of the testicular phenotype of the follicle-stimulating hormone beta-subunit knockout and the activin type II receptor knockout mice by stereological analysis. Endocrinology 142(7):2916-20. [PubMed: 11416011]  [MGI Ref ID J:71932]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	The strain originated on a B6,129 background and is currently on the same background. The investigator maintains the strain by mating homozygous males with heterozygous females. Homozygous males exhibit delayed fertility. Per Dr. Matzuk it is delayed by only a few weeks and there is no breeding problem after that. Expected coat color from breeding:Black
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

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. 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. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	100903 B6129PF2/J
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
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

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.”

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MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

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.