Description

Strain Information

Former Names C3Fe.CGr-nr/J    (Changed: 15-DEC-04 ) Type Congenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C3HeB/FeJ Donor Strain BALB/cGr Generation N32

Appearance
agouti
Related Genotype: A/A

Description
Nervous homozygotes on this C3HeB/FeJ congenic background display a mutant phenotype by 3 to 4 weeks of age, much earlier than on the BALB/cByJ background (see Stock No. 003756). Because this earlier onset occurs at wean age, the affected pups may have to stay with the mother an extra week or two. Homozygotes are somewhat smaller than their littermates and are ataxic with a slight head bobbing motion but do not display tremors. They often fall over on their side and have a sort of backwards lurching movement. They have a tendency to look up and are hyperactive compared to their littermates. Males and females are equally affected and have a normal lifespan. They are poor breeders with a higher than normal incidence of non-productive matings. A cross between C3Fe.CGr(Cg)-nr/J homozygotes and BALB/cByJ-nr/J homozygotes produced compound heterozygotes most of which presented with the nervous phenotype by 4 weeks of age, although some had onset delayed as much as to 7 weeks of age (Giggey and Thompson, 2005).

There is a 90% loss of Purkinje cells between 23 and 50 days in homozygotes. The mitochondria of all Purkinje cells become large and rounded beginning at 9 days. Subsequently most Purkinje cells degenerate. In the retina there is degeneration of the photoreceptors, which is already present at 13 days. The nearly total lack of Purkinje cells in nervous mice has been used as a tool in several investigations of the chemistry, physiology, and development of these cells.

Development
Nervous (nr) arose spontaneously at the Jackson Laboratory in the BALB/c-tk (tail kinks) stock at F4 which was imported from Dr. Hans Gruneberg in 1961. The stock was sibling mated and at F5 a single outcross to a ragged (Ra) oligosyndactly (Os) mouse of the ROP/Gn strain was made. An offspring of this cross was mated to a B6CBA hybrid and the F1 pair produced a nervous (nr/nr) male that was mated to a C57BL/6J-A^w female. A nervous (nr/nr) mouse was again crossed to a C57BL/6J-A^w and then mated to a C3H/HeJ-p^J stock by the cross intercross method to N3. Nervous was then mated to a C3H/He for 5 generations and lastly to C3HeB/FeJ. It was cryopreserved in 1987 by mating C3HeB/FeJ-nr/nr males at N31 or N32 to C3HeB/FeJ females.

Control Information

	Control
	Untyped from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying   nr allele

003756

BALB/cByJ-nr/J

View Strains carrying   nr     (1 strain)

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.

nr/nr

        involves: BALB/cGr-tk * C3HeB/JPas

• nervous system phenotype
• abnormal cerebellar Purkinje cell layer (MGI Ref ID J:106414)
  • symmetrical distribution of areas with densely packed Purkinje cells surrounded by areas lacking Purkinje cells
  • losses mainly in lateral hemispheres, 90%
  • vermis with 50% loss of Purkinje cells
  • climbing fibers synapsing on Purkinje cells in areas resistant to degeneration are relatively normal
  • climbing fibers in Purkinje cells in areas of cell loss with thickened peri-somatic plexi, few mostly atrophic fibers extending to more distal dendrites
• abnormal Purkinje cell morphology (MGI Ref ID J:23733)
  • moderate hypertrophy of terminal plexi
  • moderately thickened axons sometimes with "torpedoes"

nr/nr

        BALB/cGr-nr

• behavior/neurological phenotype
• abnormal locomotor activity (MGI Ref ID J:14906)
  • clinical signs persist from 5-6 weeks to more than a year of age
• abnormal locomotor activation (MGI Ref ID J:14906)
• hyperactivity (MGI Ref ID J:14906)
  • severity varies with the genetic background
  • behavior displays by 3.5 weeks of age but lessens with age
• ataxia (MGI Ref ID J:14906)
  • severity varies with genetic background
  • behavior displays by 3.5 weeks of age and becomes more pronounced with time
• growth/size phenotype
• decreased body size (MGI Ref ID J:14906)
  • size differential is recognizeable by two weeks of age
• cellular phenotype
• abnormal mitochondrial morphology (MGI Ref ID J:5339)
  • at 9 days after birth rounded mitochiondria are seen in perikarya of some Purkinje cells
  • by 15 days all Purkinje cells contain spherical mitochondria
• reproductive system phenotype
• reduced fertility (MGI Ref ID J:14906)
  • the abnormal neurological behavior renders both males and females poor breeders
• reduced female fertility (MGI Ref ID J:14906)
• reduced male fertility (MGI Ref ID J:14906)

View Research Applications

Research Applications

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

nr related

Neurobiology Research
Ataxia (Movement) Defects
Cerebellar Defects (Purkinje cell defect)
Tremor Defects

Sensorineural Research
Retinal Degeneration

Genes & Alleles

Gene & Allele Information

Allele Symbol		nr
Allele Name		nervous
Allele Type		Spontaneous
Common Name(s)		nervous;
Strain of Origin		BALB/cGr-tk
General Note		. There is a 90% loss of cerebellar Purkinje cells between 23 and 50 days. The mitochondria of all these cells become large and rounded beginning at 9 days. Subsequently most of them degenerate. A few reacquire normal-appearing mitochondria and survivelonger (J:5339), but some degeneration of Purkinje cells continues throughout life (J:6207). Several mitochondrial dehydrogenases were found to be histochemically normal up until the time of mitochondrial rounding (J:5399). Microtubule-associated protein-2 expression is reduced to a marked extent in adult nr/nr mice. This may, however, be a secondary effect of Purkinje cell degeneration (J:17926). Purkinje cell abnormalities are preceded by partial degeneration of cells of the external granular layer (EGL) at 6 to 8 days of age. Since normal maturation of Purkinje cells is dependent on proliferation and inward migration of EGL cells, Purkinje cell degeneration may be secondary to the EGL defect (J:12729). Some neurons in other regions of the brain alsotransiently contain spherical mitochondria, but these cells probably do not subsequently degenerate (J:5399). In the retina there is degeneration of the photoreceptors, which is already present at 13 days. Whorls of outer segment membranes form and theouter segments eventually disappear completely (J:5597). The nearly total lack of Purkinje cells in nervous mice has been used as a tool in several investigations of the chemistry, physiology, and development of these cells (J:5841, J:5619, J:5850, J:6207).

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

Chang B; Hawes NL; Hurd RE; Davisson MT; Nusinowitz S; Heckenlively JR. 2002. Retinal degeneration mutants in the mouse. Vision Res 42(4):517-25. [PubMed: 11853768]  [MGI Ref ID J:75095]

Mallet J; Huchet M; Pougeois R; Changeux JP. 1976. Anatomical, physiological and biochemical studies on the cerebellum from mutant mice. III. Protein differences associated with the weaver, staggerer and nervous mutations. Brain Res 103(2):291-312. [PubMed: 1252920]  [MGI Ref ID J:5619]

nr related

Atlas D; Teichberg VI; Changeux JP. 1977. Direct evidence for beta-adrenoreceptors on the Purkinje cells of mouse cerebellum. Brain Res 128(3):532-6. [PubMed: 18258]  [MGI Ref ID J:5841]

Bakalian A; Kopmels B; Messer A; Fradelizi D; Delhaye-Bouchaud N; Wollman E; Mariani J. 1992. Peripheral macrophage abnormalities in mutant mice with spinocerebellar degeneration. Res Immunol 143(1):129-39. [PubMed: 1565842]  [MGI Ref ID J:2228]

Baurle J; Hoshi M; Grusser-Cornehls U. 1998. Dependence of parvalbumin expression on Purkinje cell input in the deep cerebellar nuclei. J Comp Neurol 392(4):499-514. [PubMed: 9514513]  [MGI Ref ID J:118391]

Brion JP; Guilleminot J; Nunez J. 1988. Dendritic and axonal distribution of the microtubule-associated proteins MAP2 and tau in the cerebellum of the nervous mutant mouse. Brain Res Dev Brain Res 44(2):221-32. [PubMed: 3147150]  [MGI Ref ID J:17926]

Campbell DB; Hess EJ. 1996. Chromosomal localization of the neurological mouse mutations tottering (tg), Purkinje cell degeneration (pcd), and nervous (nr). Brain Res Mol Brain Res 37(1-2):79-84. [PubMed: 8738138]  [MGI Ref ID J:33012]

Chang B; Hawes NL; Hurd RE; Davisson MT; Nusinowitz S; Heckenlively JR. 2002. Retinal degeneration mutants in the mouse. Vision Res 42(4):517-25. [PubMed: 11853768]  [MGI Ref ID J:75095]

Doulazmi M; Hadj-Sahraoui N; Frederic F; Mariani J. 2002. Diminishing Purkinje cell populations in the cerebella of aging heterozygous Purkinje cell degeneration but not heterozygous nervous mice. J Neurogenet 16(2):111-23. [PubMed: 12479378]  [MGI Ref ID J:78159]

Edwards MA; Crandall JE; Leclerc N; Yamamoto M. 1994. Effects of nervous mutation on Purkinje cell compartments defined by Zebrin II and 9-O-acetylated gangliosides expression. Neurosci Res 19(2):167-74. [PubMed: 8008245]  [MGI Ref ID J:19579]

Hawes NL; Smith RS; Chang B; Davisson M; Heckenlively JR; John SW. 1999. Mouse fundus photography and angiography: a catalogue of normal and mutant phenotypes. Mol Vis 5:22. [PubMed: 10493779]  [MGI Ref ID J:59481]

Heckenlively JR; Chang B; Erway LC; Peng C; Hawes NL; Hageman GS; Roderick TH. 1995. Mouse model for Usher syndrome: linkage mapping suggests homology to Usher type I reported at human chromosome 11p15. Proc Natl Acad Sci U S A 92(24):11100-4. [PubMed: 7479945]  [MGI Ref ID J:121993]

Ikeda M; Morita I; Murota S; Sekiguchi F; Yuasa T; Miyatake T. 1993. Cerebellar nitric oxide synthase activity is reduced in nervous and Purkinje cell degeneration mutants but not in climbing fiber-lesioned mice. Neurosci Lett 155(2):148-50. [PubMed: 7690917]  [MGI Ref ID J:21353]

Jones BW; Watt CB; Frederick JM; Baehr W; Chen CK; Levine EM; Milam AH; Lavail MM; Marc RE. 2003. Retinal remodeling triggered by photoreceptor degenerations. J Comp Neurol 464(1):1-16. [PubMed: 12866125]  [MGI Ref ID J:84675]

LaVail MM; Gorrin GM; Yasumura D; Matthes MT. 1999. Increased susceptibility to constant light in nr and pcd mice with inherited retinal degenerations. Invest Ophthalmol Vis Sci 40(5):1020-4. [PubMed: 10102304]  [MGI Ref ID J:53937]

LaVail MM; White MP; Gorrin GM; Yasumura D; Porrello KV; Mullen RJ. 1993. Retinal degeneration in the nervous mutant mouse. I. Light microscopic cytopathology and changes in the interphotoreceptor matrix. J Comp Neurol 333(2):168-81. [PubMed: 7688384]  [MGI Ref ID J:12820]

LaVail MW; Yasumura D; Matthes MT; Lau-Villacorta C; Unoki K; Sung CH; Steinberg RH. 1998. Protection of mouse photoreceptors by survival factors in retinal degenerations. Invest Ophthalmol Vis Sci 39(3):592-602. [PubMed: 9501871]  [MGI Ref ID J:46230]

Lalonde R; Strazielle C. 2003. Motor coordination, exploration, and spatial learning in a natural mouse mutation (nervous) with Purkinje cell degeneration. Behav Genet 33(1):59-66. [PubMed: 12645822]  [MGI Ref ID J:81630]

Lalonde R; Strazielle C. 2007. Spontaneous and induced mouse mutations with cerebellar dysfunctions: behavior and neurochemistry. Brain Res 1140:51-74. [PubMed: 16499884]  [MGI Ref ID J:120621]

Landis SC. 1973. Changes in neuronal mitochondrial shape in brains of nervous mutant mice. J Hered 64(4):193-6. [PubMed: 4766206]  [MGI Ref ID J:5399]

Landis SC. 1975. Histochemical demonstration of mitochondrial dehydrogenases in developing normal and nervous mutant mouse Purkinje cells. J Histochem Cytochem 23(2):136-43. [PubMed: 1117128]  [MGI Ref ID J:5523]

Landis SC. 1973. Ultrastructural changes in the mitochondria of cerebellar Purkinje cells of nervous mutant mice. J Cell Biol 57(3):782-97. [PubMed: 4698906]  [MGI Ref ID J:5339]

Li J; Imitola J; Snyder EY; Sidman RL. 2006. Neural stem cells rescue nervous purkinje neurons by restoring molecular homeostasis of tissue plasminogen activator and downstream targets. J Neurosci 26(30):7839-48. [PubMed: 16870729]  [MGI Ref ID J:111061]

Li J; Ma Y; Teng YD; Zheng K; Vartanian TK; Snyder EY; Sidman RL. 2006. Purkinje neuron degeneration in nervous (nr) mutant mice is mediated by a metabolic pathway involving excess tissue plasminogen activator. Proc Natl Acad Sci U S A 103(20):7847-52. [PubMed: 16682647]  [MGI Ref ID J:110097]

Mallet J; Huchet M; Pougeois R; Changeux JP. 1976. Anatomical, physiological and biochemical studies on the cerebellum from mutant mice. III. Protein differences associated with the weaver, staggerer and nervous mutations. Brain Res 103(2):291-312. [PubMed: 1252920]  [MGI Ref ID J:5619]

Milner TE; Cadoret G; Lessard L; Smith AM. 1995. EMG analysis of harmaline-induced tremor in normal and three strains of mutant mice with Purkinje cell degeneration and the role of the inferior olive. J Neurophysiol 73(6):2568-77. [PubMed: 7666163]  [MGI Ref ID J:29602]

Miret-Duvaux O; Frederic F; Simon D; Guenet JL; Hanauer A; Delhaye-Bouchaud N; Mariani J. 1990. Glutamate dehydrogenase in cerebellar mutant mice: gene localization and enzyme activity in different tissues. J Neurochem 54(1):23-9. [PubMed: 2293612]  [MGI Ref ID J:10148]

Mishra PR; Jain VK; Bijlani V; Grewal MS. 1983. DNA loss in the developing cerebellum of nervous mouse: a flow cytometric study. Brain Res 282(2):193-6. [PubMed: 6831242]  [MGI Ref ID J:12729]

Mullen RJ; LaVail M. 1975. Two types of retinal degeneration in cerebellar mutant mice. Nature 258(5535):528-30. [PubMed: 1196386]  [MGI Ref ID J:5597]

Ren J; Stubbs EB Jr; Matthes MT; Yasumura D; Naash MI; LaVail MM; Peachey NS. 2001. Retinal Degeneration in the nervous Mutant Mouse. IV. Inner Retinal Changes. Exp Eye Res 72(3):243-52. [PubMed: 11180973]  [MGI Ref ID J:67788]

Ren JC; LaVail MM; Peachey NS. 2000. Retinal degeneration in the nervous mutant mouse. III. Electrophysiological studies of the visual pathway. Exp Eye Res 70(4):467-73. [PubMed: 10865995]  [MGI Ref ID J:62317]

Rossi F; Jankovski A; Sotelo C. 1995. Target neuron controls the integrity of afferent axon phenotype: a study on the Purkinje cell-climbing fiber system in cerebellar mutant mice. J Neurosci 15(3 Pt 1):2040-56. [PubMed: 7891151]  [MGI Ref ID J:23733]

Schmidt MJ; Nadi NS. 1977. Cyclic nucleotide accumulation in vitro in the cerebellum of 'nervous' neurologically mutant mice. J Neurochem 29(1):87-90. [PubMed: 18558]  [MGI Ref ID J:5850]

Sidman RL; Green MC. 1970. "Nervous," a new mutant mouse with cerebellar disease. Coll Int Centre Natl Recherche Sci 924:69-79.  [MGI Ref ID J:14906]

Sotelo C; Triller A. 1979. Fate of presynaptic afferents to Purkinje cells in the adult nervous mutant mouse: a model to study presynaptic stabilization. Brain Res 175(1):11-36. [PubMed: 487138]  [MGI Ref ID J:6207]

Wassef M; Sotelo C; Cholley B; Brehier A; Thomasset M. 1987. Cerebellar mutations affecting the postnatal survival of Purkinje cells in the mouse disclose a longitudinal pattern of differentially sensitive cells. Dev Biol 124(2):379-89. [PubMed: 3678603]  [MGI Ref ID J:106414]

White MP; Gorrin GM; Mullen RJ; LaVail MM. 1993. Retinal degeneration in the nervous mutant mouse. II. Electron microscopic analysis. J Comp Neurol 333(2):182-98. [PubMed: 8345102]  [MGI Ref ID J:12821]

Yamamoto M; Schwarting GA; Crandall JE. 1994. Altered 9-O acetylation of disialogangliosides in cerebellar Purkinje cells of the nervous mutant mouse. Brain Res 662(1-2):223-32. [PubMed: 7859075]  [MGI Ref ID J:21089]

Zanjani H; Herrup K; Mariani J. 2004. Cell number in the inferior olive of nervous and leaner mutant mice. J Neurogenet 18(1):327-39. [PubMed: 15370195]  [MGI Ref ID J:101982]

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

Control Information

	Control
	Untyped from the colony
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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phone:	207-288-6470
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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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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.