Description

Strain Information

Former Names B6129S/Sv-Dnahc11iv/J    (Changed: 15-DEC-04 ) Type Mutant Stock; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N1F1N1p

Description
DNAHC11 is important for developmental control of organ positioning in the left-right axis such that homozygosity for the situs inversus viscerum (iv) mutant allele can result not only in inverse placement of the visceral and thoracic organs, but also in anomalous positioning and interactions of blood vessels (including the hepatic portal, inferior vena cava, and azygos vein) and modified shape of organs and blood vessels, including abnormal lobation of lungs or liver. Approximately 50% of mice homozygous for Dnahc11^iv have situs inversus, and the likelihood of situs inversus is not impacted by whether the homozygous parent has situs inversus. This indicates that wild type Dnahc11 instructs left-right asymmetry, and in the absence of functional Dnahc11 the direction of this asymmetry is random. Heterotaxia is found in less than half of homozygotes and occurs equally in those that do and do not have situs inversus. While heterotaxia may be impacted by genetic background, the incidence of situs inversus has not shown this variation. Situs inversus can be identified shortly after birth, until the skin thickens at approximately day 5, by viewing the location of the milk-filled stomach through the skin. Homozygotes are generally viable and do breed, although poorreproductive performance with a high rate of resorption has been reported by Brown et al. (Development 1989). Some premature death has been reported and may be caused by deformities of the cardiac loop. (Hummel and Chapman, 1959; Layton 1976; Brown et al., 1989; Icardo and Colvee, 2001.)

Development
In 1956 Katherine Hummel reported finding situs inversus viscerum (iv) in 6 out of 42 mice in the F3 generation from a cross of a C3H/e female with an my/my male. This my/my male was likely from the line that was then being inbred to become My/Hu (see stock#000265). The my mutation was bred out of this new mutant stock and in 1972 the iv-bearing stock was transferred from Katherine Hummel to Robert Collins, both at The Jackson Laboratory. Collins began inbreeding from the outbred stock in 1975 and this generated the strain SI/Col (see stock#001045) which is homozygous for Dnahc11^iv, a, and Tyrp1^b. SI/Col reached F62 in 1994. At some point the Dnahc11^iv mutation was bred onto 129/Sv-ter but the details of this breeding have been lost. In 1981 males homozygous for Dnahc11^iv on the 129/Sv-ter background were bred to C57BL/6J females to generate embryos for cryopreservation.

Control Information

		These serve as only approximate controls for this stock, in which alleles derived from the two parental strains are assorting randomly throughout the genome.
Considerations for Choosing Controls

Related Strains

Strains carrying   Dnahc11^iv allele

001045

SI/Col Tyrp1b Dnahc11iv/J

View Strains carrying   Dnahc11^iv     (1 strain)

Additional Web Information

Congenic Nomenclature
JAX^® NOTES, Winter 1993; 452. The Situs Inversus (iv) Mutation.

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.

Dnahc11^iv/Dnahc11^iv

        SI/Col Tyrp1^b Dnahc11^iv/J

• cardiovascular system phenotype
• abnormal cardiovascular system morphology (MGI Ref ID J:4058)
  • homozygotes exhibit various cardiovascular, spleen and liver defects that may or may not co-occur in the same mouse
  • 7.6% display cardiac lesions, which are more common in females (11.5%) than in males (3.1%) and in fetuses (16%) than in adults (3.6%)
• abnormal heart atrium morphology (MGI Ref ID J:4058)
  • 50.2% exhibit mirror-image arrangement of the atrial appendages
  • 3.3% have left atrial isomerism
  • incidence of isomerism of the atrial appendages is significantly higher in females (7.4%) than in males (1.6%) and in fetuses (12%) than in adults (1.4%)
• right atrial isomerism (MGI Ref ID J:4058)
  • 1.5% have right atrial isomerism
• abnormal vein morphology (MGI Ref ID J:4058)
  • 26.6% exhibit a ventral portal vein, with the incidence of the ventral location significantly higher in females (33.1%) than in males (18.9%)
• abnormal inferior vena cava morphology (MGI Ref ID J:4058)
  • 17.8% show an abnormal connection of the inferior caval vein, with the abnormal arrangement more common in fetuses (29.3%) than in adults (15%)
• growth/size phenotype
• right atrial isomerism (MGI Ref ID J:4058)
  • 1.5% have right atrial isomerism
• situs inversus (MGI Ref ID J:4058)
  • seen in about 50% of homozygotes
• hematopoietic system phenotype
• abnormal spleen morphology (MGI Ref ID J:4058)
  • 36.4% exhibit an abnormal spleen, which is seen more often in females (44.6%) than in males (26.8%)
  • spleen abnormalities include fissured, bilobed, elongated or absent spleen
• immune system phenotype
• abnormal spleen morphology (MGI Ref ID J:4058)
  • 36.4% exhibit an abnormal spleen, which is seen more often in females (44.6%) than in males (26.8%)
  • spleen abnormalities include fissured, bilobed, elongated or absent spleen
• liver/biliary system phenotype
• abnormal liver morphology (MGI Ref ID J:4058)
  • abnormal arrangement of the liver, which is more common in females (42.6%) than in males (26.8%)
• embryogenesis phenotype
• abnormal embryo implantation (MGI Ref ID J:4058)
  • females with bilobed or fissured spleens or with abnormal livers have fewer implantation sites than those with normal spleens and livers

View Research Applications

Research Applications

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

Dnahc11^iv related

Developmental Biology Research
Internal/Organ Defects (heart: vasculature)
Internal/Organ Defects (situs inversus)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Dnahc11iv
Allele Name		situs inversus viscerum
Allele Type		Spontaneous
Common Name(s)		iv;
Strain of Origin		(C3HeB/Fe x STOCK Frem2)F3
Gene Symbol and Name		Dnahc11, dynein, axonemal, heavy chain 11
Chromosome		12
Gene Common Name(s)		CILD7; DNAHBL; DNHBL; DPL11; FLJ30095; FLJ37699; iv; lrd; situs inversus viscerum;
General Note		About 50 per cent of homozygotes showed left-right transposition of stomach and abdominal viscera. About half of all the homozygotes showed discordance in asymmetry between the stomach and the major abdominal and thoracic veins, the discordance occurringwith similar frequency in mice with normal and reversed viscera. In the stock examined by Hummel and Chapman (J:212) penetrance was found to be 71 per cent when mice were classified by both these criteria. Layton (J:5788) has postulated that the wild-type allele of the Dnahc11 locus is necessary for development of the normal asymmetrical configuration of the viscera. In iv/iv mice, this control is absent, allowing random direction of the asymmetry and thus accounting for the fact that only 50 per cent ofthe homozygotes show reversed asymmetry.
Molecular Note		A G-to-A transition mutation led to a substitution of a glutamate to a lysine in the encoded protein. This residue is located between the second and third P-loop motifs, a highly conserved region that constitutes the motor domain. [MGI Ref ID J:44093]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Icardo JM; Colvee E. 2001. Origin and course of the coronary arteries in normal mice and in iv/iv mice. J Anat 199(Pt 4):473-82. [PubMed: 11693308]  [MGI Ref ID J:73207]

Layton WM Jr. 1976. Random determination of a developmental process: reversal of normal visceral asymmetry in the mouse. J Hered 67(6):336-8. [PubMed: 1021593]  [MGI Ref ID J:5788]

Oh SP; Li E. 2002. Gene-dosage-sensitive genetic interactions between inversus viscerum (iv), nodal, and activin type IIB receptor (ActRIIB) genes in asymmetrical patterning of the visceral organs along the left-right axis. Dev Dyn 224(3):279-90. [PubMed: 12112458]  [MGI Ref ID J:78247]

Supp DM; Witte DP; Potter SS; Brueckner M. 1997. Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice. Nature 389(6654):963-6. [PubMed: 9353118]  [MGI Ref ID J:44093]

Dnahc11^iv related

Adachi H; Saijoh Y; Mochida K; Ohishi S; Hashiguchi H; Hirao A; Hamada H. 1999. Determination of left/right asymmetric expression of nodal by a left side-specific enhancer with sequence similarity to a lefty-2 enhancer. Genes Dev 13(12):1589-600. [PubMed: 10385627]  [MGI Ref ID J:56146]

Campione M; Ros MA; Icardo JM; Piedra E; Christoffels VM; Schweickert A; Blum M; Franco D; Moorman AF. 2001. Pitx2 expression defines a left cardiac lineage of cells: evidence for atrial and ventricular molecular isomerism in the iv/iv mice. Dev Biol 231(1):252-64. [PubMed: 11180966]  [MGI Ref ID J:67751]

Franco D; Kelly R; Moorman AF; Lamers WH; Buckingham M; Brown NA. 2001. MLC3F transgene expression in iv mutant mice reveals the importance of left-right signalling pathways for the acquisition of left and right atrial but not ventricular compartment identity. Dev Dyn 221(2):206-15. [PubMed: 11376488]  [MGI Ref ID J:69780]

Golding JP; Partridge TA; Beauchamp JR; King T; Brown NA; Gassmann M; Zammit PS. 2004. Mouse myotomes pairs exhibit left-right asymmetric expression of MLC3F and alpha-skeletal actin. Dev Dyn 231(4):795-800. [PubMed: 15499557]  [MGI Ref ID J:93818]

Hummel KP; Chapman D. 1956. Situs Viscerum Inversus Mouse News Lett 14:21.  [MGI Ref ID J:24771]

Hummel KP; Chapman DB. 1959. Visceral inversion and associated anomalies in the mouse J Hered 50:9-13.  [MGI Ref ID J:212]

Icardo JM; Colvee E. 2001. Origin and course of the coronary arteries in normal mice and in iv/iv mice. J Anat 199(Pt 4):473-82. [PubMed: 11693308]  [MGI Ref ID J:73207]

Kawakami R; Dobi A; Shigemoto R; Ito I. 2008. Right isomerism of the brain in inversus viscerum mutant mice. PLoS ONE 3(4):e1945. [PubMed: 18414654]  [MGI Ref ID J:134302]

Layton WM Jr. 1976. Random determination of a developmental process: reversal of normal visceral asymmetry in the mouse. J Hered 67(6):336-8. [PubMed: 1021593]  [MGI Ref ID J:5788]

Layton WM; Layton MW; Binder M; Kurnit DM; Hanzlik AJ; Van Keuren M; Biddle FG. 1993. Expression of the IV (reversed and/or heterotaxic) phenotype in SWV mice. Teratology 47(6):595-602. [PubMed: 8367832]  [MGI Ref ID J:11908]

Lowe LA; Supp DM; Sampath K; Yokoyama T; Wright CV; Potter SS; Overbeek P; Kuehn MR. 1996. Conserved left-right asymmetry of nodal expression and alterations in murine situs inversus [see comments] Nature 381(6578):158-61. [PubMed: 8610013]  [MGI Ref ID J:32936]

Matin A; Collin GB; Varnum DS; Nadeau JH. 1998. Testicular teratocarcinogenesis in mice--a review. APMIS 106(1):174-82. [PubMed: 9524576]  [MGI Ref ID J:46683]

Meno C; Ito Y; Saijoh Y; Matsuda Y; Tashiro K; Kuhara S; Hamada H. 1997. Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos. Genes Cells 2(8):513-24. [PubMed: 9348041]  [MGI Ref ID J:49270]

Meno C; Saijoh Y; Fujii H; Ikeda M; Yokoyama T; Yokoyama M; Toyoda Y; Hamada H. 1996. Left-right asymmetric expression of the TGF beta-family member lefty in mouse embryos. Nature 381(6578):151-5. [PubMed: 8610011]  [MGI Ref ID J:32932]

Metzger RJ; Klein OD; Martin GR; Krasnow MA. 2008. The branching programme of mouse lung development. Nature 453(7196):745-50. [PubMed: 18463632]  [MGI Ref ID J:136198]

Meyer RA; Cohen MF; Recalde S; Zakany J; Bell SM; Scott WJ Jr; Lo CW. 1997. Developmental regulation and asymmetric expression of the gene encoding Cx43 gap junctions in the mouse limb bud. Dev Genet 21(4):290-300. [PubMed: 9438343]  [MGI Ref ID J:45219]

Nakamura T; Mine N; Nakaguchi E; Mochizuki A; Yamamoto M; Yashiro K; Meno C; Hamada H. 2006. Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system. Dev Cell 11(4):495-504. [PubMed: 17011489]  [MGI Ref ID J:119676]

Novobrantseva TI; Martin VM; Pelanda R; Muller W; Rajewsky K ; Ehlich A. 1999. Rearrangement and expression of immunoglobulin light chain genes can precede heavy chain expression during normal B cell development in mice. J Exp Med 189(1):75-88. [PubMed: 9874565]  [MGI Ref ID J:52061]

Oh SP; Li E. 2002. Gene-dosage-sensitive genetic interactions between inversus viscerum (iv), nodal, and activin type IIB receptor (ActRIIB) genes in asymmetrical patterning of the visceral organs along the left-right axis. Dev Dyn 224(3):279-90. [PubMed: 12112458]  [MGI Ref ID J:78247]

Okada Y; Nonaka S; Tanaka Y; Saijoh Y; Hamada H; Hirokawa N. 1999. Abnormal nodal flow precedes situs inversus in iv and inv mice. Mol Cell 4(4):459-68. [PubMed: 10549278]  [MGI Ref ID J:109561]

Okada Y; Takeda S; Tanaka Y; Belmonte JC; Hirokawa N. 2005. Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination. Cell 121(4):633-44. [PubMed: 15907475]  [MGI Ref ID J:98946]

Piedra ME; Icardo JM; Albajar M; Rodriguez-Rey JC; Ros MA. 1998. Pitx2 participates in the late phase of the pathway controlling left-right asymmetry. Cell 94(3):319-24. [PubMed: 9708734]  [MGI Ref ID J:49089]

Saijoh Y; Adachi H; Sakuma R; Yeo CY; Yashiro K; Watanabe M; Hashiguchi H; Mochida K; Ohishi S; Kawabata M; Miyazono K; Whitman M; Hamada H. 2000. Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2. Mol Cell 5(1):35-47. [PubMed: 10678167]  [MGI Ref ID J:60152]

Saijoh Y; Oki S; Tanaka C; Nakamura T; Adachi H; Yan YT; Shen MM; Hamada H. 2005. Two nodal-responsive enhancers control left-right asymmetric expression of Nodal. Dev Dyn 232(4):1031-6. [PubMed: 15736223]  [MGI Ref ID J:97079]

Seo JW; Brown NA; Ho SY; Anderson RH. 1992. Abnormal laterality and congenital cardiac anomalies. Relations of visceral and cardiac morphologies in the iv/iv mouse. Circulation 86(2):642-50. [PubMed: 1638728]  [MGI Ref ID J:4058]

Supp DM; Witte DP; Potter SS; Brueckner M. 1997. Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice. Nature 389(6654):963-6. [PubMed: 9353118]  [MGI Ref ID J:44093]

Tanaka Y; Okada Y; Hirokawa N. 2005. FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination. Nature 435(7039):172-7. [PubMed: 15889083]  [MGI Ref ID J:98555]

Vermot J; Pourquie O. 2005. Retinoic acid coordinates somitogenesis and left-right patterning in vertebrate embryos. Nature 435(7039):215-20. [PubMed: 15889094]  [MGI Ref ID J:98584]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

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. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. 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. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

		These serve as only approximate controls for this stock, in which alleles derived from the two parental strains are assorting randomly throughout the genome.
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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JAX^® Mice & Services Conditions of Use

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