Description

Strain Information

Type Congenic; Mutant Strain; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6J Donor Strain Cacna1atg-la: AKR/J; Os: (101 x C3H)F1 Generation N14F54pN1

Appearance
black, fused digits
Related Genotype: a/a Os +/+ ? or a/a Os +/+ Cacnala^tg-la

black, ataxic
Related Genotype: a/a + Cacnala^tg-la/+ Cacnala^tg-la

Description
Mice homozygous for the leaner spontaneous mutation (Cacna1a^tg-la) begin to show ataxia, stiffness, and retarded motor activity by 8 to 10 days of age. Many homozygous mutant mice die by weaning age, but some survive, and females may even breed. Homozygous mutant adults are characterized by instability of the trunk and hypertonia of the trunk and limb muscles. Seizures have not been observed. The cerebellum is reduced in size, particularly in the anterior region. There is loss of granule cells beginning at 10 days of age and loss of Purkinje and Golgi cells beginning after 1 month.

Leaner/tottering heterozygotes (Cacna1a^tg-la/Cacna1a^tg) show ataxia, stiffness, and retarded motor activity at 15 to 17 days of age. Within a few days, they develop a wobbly gait and intermittent focal seizures which continue throughout life. The cerebellum shows shrinkage and degenerative changes of the Purkinje cells.

Development
The leaner allele (Cacna1a^tg-la) arose spontaneously in strain AKR/J at The Jackson Laboratory in 1960. It was backcrossed onto strain C57BL/6J reaching N10 in 1969. It was then crossed to the Sox18^Ra/+ Os/+ Pt/+ strain probably on C57BL/6By. A very close linkage was found between leaner (Cacna1a^tg-la) and Os on Chromosome 8 and the balanced stock Os +/+ Cacna1a^tg-la was developed. It was sib mated by always selecting the Os phenotype and cryopreserved in 1985 by mating Os +/+ ? at N13 or N14F3 to C57BL/6J females.

Control Information

	Control
	Os +/+ ?
Considerations for Choosing Controls

Related Strains

Strains carrying   Os allele

003523	B6.ROP/Le-Os/J
000125	B6By.Cg-Sox18Ra Pt Os/J
000300	MYD/Le-Os +/+ Largemyd/J
000267	ROP/GnLeJ
002503	ROP/Le-Os Es1a/+ Es1a/J

View Strains carrying   Os     (5 strains)

Strains carrying other alleles of Cacna1a

008623	B10(Cg)-Cacna1aTg-5J/LetJ
008622	B6.C3Bir-Cacna1atg-4J/LetJ
000544	B6.D2-Cacna1atg/J
005520	B6;CByJ-Cacna1atg-6J/J

View Strains carrying other alleles of Cacna1a     (4 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Cacna1a^tg-la/Cacna1a^tg-la

        B6.Cg-Os +/+ Cacna1a^tg-la/J

• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:72853)
  • activation threshold and conduction velocity of L5 dorsal root evoked by electrical stimulation of the sciatic nerve are not significantly different from those of wild-type
  • the dose-repsonse curves for opioid peptide impact on dorsal root-evokes slow ventral root potential is normal
• abnormal action potential (MGI Ref ID J:72853)
  • although the capsaicin-sensitive component in C-fiber response is not significantly afffected, homozygotes are less sensitive to inhibition of femoral nerve-evoked slow ventral root potential by tachykinin NK1 receptor agonist GR82334
  • femoral nerve-evoked peak amplitudes of dorsal root potentials are smaller than in wild-type controls but are inhibited by GABAa receptor antagonist bucuculline to a similar extent. The slow component of the dorsal root potential is smaller and does not increase with increased pulse width
• abnormal channel response (MGI Ref ID J:72853)
  • electrical stimulation of a dorsal root at C-fiber strength gives slow ventral root potentials and monosynaptic reflexes that are not diminished by a P/Q-type channel blocker but are diminished by an N-type channel blocker indicating an absence of a P/Q-type channel component in the response
• abnormal nerve fiber response (MGI Ref ID J:72853)
  • tachykinin receptor antagonist GR82334 is less inhibitory of the femoral nerve-evoked slow verntral root depolarization than in wild-type controls
• decreased nerve fiber response intensity (MGI Ref ID J:72853)
  • electrical stimulation of dorsal roots at C-fiber strength yileds a slightly smaller amplitude of monosynaptic reflux and integrated area of slow ventral root potential than in wild-type mice
• touch/vibrissae phenotype
• decreased thermal nociceptive threshold (MGI Ref ID J:72853)
  • enhanced thermal responses are found in paw flick and tail flick assays compared with wild-type and heterozygotes
• hyporesponsive to tactile stimuli (MGI Ref ID J:72853)
  • decreased frequency of foot withdrawals in response to a defined mechanical stimulus with calebrated Von Frey hairs
• behavior/neurological phenotype
• decreased thermal nociceptive threshold (MGI Ref ID J:72853)
  • enhanced thermal responses are found in paw flick and tail flick assays compared with wild-type and heterozygotes
• hyporesponsive to tactile stimuli (MGI Ref ID J:72853)
  • decreased frequency of foot withdrawals in response to a defined mechanical stimulus with calebrated Von Frey hairs

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

Os/Os⁺

        involves: 101 * C3H * CBA/Gr

• lethality-prenatal/perinatal
• prenatal lethality (MGI Ref ID J:13049)
• limbs/digits/tail phenotype
• abnormal carpal bone morphology (MGI Ref ID J:13049)
  • ulnar end of the hamatum articulates with metacarpal 4, but does not reach metacarpal 5
  • metacarpal 5 is in a fixed state of abduction
• fused carpal bones (MGI Ref ID J:13049)
  • extensive fusions in carpus
• abnormal foot plate morphology (MGI Ref ID J:12942)
  • beginning at E11 the preaxial border of the foot plate is flattened, displaying an ovoid rather than circular outline
  • blastemata are crowded and small
  • interdigital area between digits 2 and 3 is reduced by E13
  • in most cases, digit 2 is formed closer to and may fuse to digit 3
• abnormal tarsus morphology (MGI Ref ID J:13049)
  • extensive and varied fusions in tarsus, which includes a solid fusion between talus and calcaneus
  • calcaneus frequently lacks process trochlearis
  • fusion occurs between the naviculare and a composite of cuneiforme 3 and cuboideum in all animals
  • naviculare is narrow as compared to wildtype
  • long axis of calcaneus and metararsalia are not parallel, as a result hindfeet point outward
• oligodactyly (MGI Ref ID J:13049)
  • digits 2 and 3 are typically involved
  • different digits in the same foot can be both polydactylous and oligodactylous
  • digit loss arises by fusion of digits 2 and 3, however, digit 2 is often thinner than normal and may vanish without fusion to digit 3
• polydactyly (MGI Ref ID J:13049)
  • exhibited in the hindfeet of some animals
  • different digits in the same foot can be both polydactylous and oligodactylous
• polysyndactyly (MGI Ref ID J:13049)
  • exhibited in some animals
• syndactyly (MGI Ref ID J:13049)
  • all four feet are affected, although the forefeet are less severely affected than the hindfeet
  • syndactylism primarily involves digits 2 and 3
  • nearly all animals exhibit osseous fusions of the bases of metacarpalia or metatarsalia 4 and 5
  • some animals exhibit fusion of metatarsalia 1 and 2
  • most fusions are secondary, only a few of the fusions are primary hard tissue in both embryo and adult
  • in the tarsus, only the cuneiforme 3 and cuboideum fusion is primary
  • hard tissue fusions start at the basal phalanges and spread distally
  • all fusions between metacarpal and metatarsals are secondary
• polysyndactyly (MGI Ref ID J:13049)
  • exhibited in some animals
• skeleton phenotype
• abnormal carpal bone morphology (MGI Ref ID J:13049)
  • ulnar end of the hamatum articulates with metacarpal 4, but does not reach metacarpal 5
  • metacarpal 5 is in a fixed state of abduction
• fused carpal bones (MGI Ref ID J:13049)
  • extensive fusions in carpus
• abnormal tarsus morphology (MGI Ref ID J:13049)
  • extensive and varied fusions in tarsus, which includes a solid fusion between talus and calcaneus
  • calcaneus frequently lacks process trochlearis
  • fusion occurs between the naviculare and a composite of cuneiforme 3 and cuboideum in all animals
  • naviculare is narrow as compared to wildtype
  • long axis of calcaneus and metararsalia are not parallel, as a result hindfeet point outward
• embryogenesis phenotype
• abnormal embryonic tissue morphology (MGI Ref ID J:13049)
  • at E14 projections of digits 2 and 3 at the edge of the foot plate are closer together than wildtype and there is only a single basal phalanx common to both digits
  • at E14-5 cuneiforme 3 and cuboideum have fused to a single element and are elongated in a diagonal direction rather than circular
  • at E16 metacarpalia 4 and 5 are fused
• abnormal mesenchyme morphology (MGI Ref ID J:12942)
  • a reduction in the amount of mesenchyme in the preaxial area of the foot plate is observed by E13

Os/Os⁺

        ROP/GnLeJ

• renal/urinary system phenotype
• abnormal kidney morphology (MGI Ref ID J:3842)
  • renal mass is reduced by 38% in comparison to wild-type
  • in nephrectomized heterozygote males, compensatory kidney growth is reduced in comparison to control
• abnormal kidney collecting duct (MGI Ref ID J:3842)
  • the principal cell type in the collecting duct is hypertrophied, with the greatest degree of hypertrophy in the nephrectomized heterozygotes
• abnormal renal glomerulus morphology (MGI Ref ID J:3842)
  • size of glomeruli is slightly increased in left kidney following unilateral nephrectomy as compared to control
• decreased renal glomerulus number (MGI Ref ID J:3842)
  • midtranverse sections from the left kidney indicate that glomeruli density is reduced by 50% in heterozygotes
• abnormal renal tubule morphology (MGI Ref ID J:3842)
  • diameters of the proximal convoluted and straight tubules are increased in size as compared to wild-type
  • tubular epithelial cells are hypertrophied in both heterozyote and nephrectomized heterozygotes, however, the magnitude of hypertrophy is increased in unaltered mice
• abnormal proximal convoluted tubule morphology (MGI Ref ID J:3842)
  • segments of proximal tubule, especially pars recta, exhibit hypertrophy
• polyuria (MGI Ref ID J:3842)
  • rate of urine flow is increased in heterozygotes as compared to controls, however glomerular filtration rate is not affected
  • excretion of creatinine, sodium and potassium is similar to control
• homeostasis/metabolism phenotype
• increased blood urea nitrogen level (MGI Ref ID J:3842)
  • BUN levels are increased by almost 50% in both heterozyote and nephrectomized heterozygotes as compared to controls

View Research Applications

Research Applications

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

Cacna1a^tg-la related

Cell Biology Research
Channel and Transporter Defects (calcium)

Mouse/Human Gene Homologs
migraine, familial hemiplegic, with progressive cerebellar ataxia

Neurobiology Research
Ataxia (Movement) Defects
Cerebellar Defects
Channel and Transporter Defects (calcium)
Neurodegeneration

Os related

Developmental Biology Research
Skeletal Defects

Internal/Organ Research
Kidney Defects (diabetes insipidus)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cacna1atg-la
Allele Name		leaner
Allele Type		Spontaneous
Common Name(s)		Cacna1ala; Ln; tgla;
Strain of Origin		AKR/J
Gene Symbol and Name		Cacna1a, calcium channel, voltage-dependent, P/Q type, alpha 1A subunit
Chromosome		8
Gene Common Name(s)		APCA; BccA1; CACNL1A4; CAV2.1; Ccha1a; EA2; FHM; HPCA; MHP; MHP1; SCA6; alpha1A; calcium channel alpha 1a; la; leaner; neuroscience mutagenesis facility, 352; nmf352; rbA-1; rkr; rocker; tg; tottering;
General Note		Cacna1atg-la, leaner, recessive. The leaner mutation arose spontaneously in the AKR/J strain. Homozygotes are recognized at 8 to 10 days of age by ataxia, stiffness, and retarded motor activity. Adults are characterized by instability of the trunk, and hypertonia of trunk and limb muscles. Seizures have not been observed (J:28459). Heterozygous Cacna1atg-la/Cacna1atg mice show ataxia, stiffness, and retarded motor activity at 15 to 17 days of age. Within a few days they develop a wobbly gait and intermittent focal seizures that continue throughout life (J:5240).The cerebellum is reduced in size, particularly in the anterior region, in Cacna1atg-la homozygous mice (J:28459). There is loss of granule cells beginning at 10 days of age and loss of Purkinje and Golgi cells beginning after 1 month. Cell loss later slows but continues throughout life. Granule and Purkinje cells are more severely affected than Golgi cells and the anterior folia more severely affectedthan other parts of the cerebellum (J:6909). Heckroth and Abbott (J:20921) found loss of Purkinje cells from alternating sagittal zones of the cerebellum in Cacna1atg-la homozygotes.The cerebellum of Cacna1atg-la/Cacna1atg heterozygotes shows shrinkage and degenerative changes of the Purkinje cells (J:5240). The loss in cerebellar volume in these and in homozygous Cacna1atg mice is specific to the molecular layer, with no change in volume of the granule cell or white matter layers (J:22482).Many Cacna1atg-la homozygotes die at weaning time, but some survive and females may breed (J:28459).
Molecular Note		A nucleotide substitution in the splice donor sequence of Cacna1a in leaner mice could cause the aberrant transcripts found in these mice. [MGI Ref ID J:36596]
Allele Symbol		Os
Allele Name		Os
Allele Type		Radiation induced
Strain of Origin		(101 x C3H)F1
General Note		This mutation arose in an irradiation experiment and was probably X-ray induced. Homozygotes die by the fifth day of embryonic life, shortly after the 64-cell stage, as a result of abnormalities occurring during the seventh and eighth divisions (J:5017).There is a very high mitotic index, more than a third of the cells containing mitotic figures. Os in homozygotes may exert its primary effect on the mitotic apparatus (J:5768). Heterozygotes are affected on all four feet. Fusion usually occurs between the second and third digits and occasionally involves the fourth (J:13049). The muscles of the forearms and lower legs as well as of the feet show anomalous arrangements not necessarily correlated with the skeletal changes (J:12944). At 11 days of gestation the preaxial border of the limbs can be seen to be reduced (J:12942), and a histological examination at this time shows that there is a small amount of cellular degeneration in the preaxial part of the footplate mesoderm, leading to coalescence of thesecond and third digital rudiments (J:5107). Os /+ mice have a mild diabetes insipidus present at 5 weeks and increasing with age. In combination with one or more recessive modifying genes in the selected DI stock, Os/+ mice have a severe diabetes insipidus (J:12948). The cause of the diabetes is a 45% reduction in size of the kidneys with an 80% reduction in number of glomeruli. Compensatory hypertrophy of the nephrons is not sufficient to restore normal urine-concentrating ability (J:5127)(J:5128). Itis not known how the kidney and foot defects are related, or how either is related to the early death of the homozygote.
Molecular Note		The oligosyndactylism mutation is due to a chromosomal inversion that has breakpoints approximately 10 Mb apart. One breakpoint appears to reside in the Anapc10 gene, and an aberrant transcript consisting of part of Anapc10 and an unrelated sequence is expressed at low levels. [MGI Ref ID J:81567] [MGI Ref ID J:95333]

Genotyping

Genotyping Information

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

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Meier H; MacPike AD. 1971. Three syndromes produced by two mutant genes in the mouse. Clinical, pathological, and ultrastructural bases of tottering, leaner, and heterozygous mice. J Hered 62(5):297-302. [PubMed: 4941467]  [MGI Ref ID J:5240]

Yoon CH. 1969. Disturbances in developmental pathways leading to a neurological disorder of genetic origin, leaner, in mice. Dev Biol 20(2):158-81. [PubMed: 5799428]  [MGI Ref ID J:5121]

Additional References

Zwingman TA; Neumann PE; Noebels JL; Herrup K. 2001. Rocker is a new variant of the voltage-dependent calcium channel gene Cacna1a. J Neurosci 21(4):1169-78. [PubMed: 11160387]  [MGI Ref ID J:71860]

Cacna1a^tg-la related

Alonso I; Marques JM; Sousa N; Sequeiros J; Olsson IA; Silveira I. 2008. Motor and cognitive deficits in the heterozygous leaner mouse, a Cav2.1 voltage-gated Ca2+ channel mutant. Neurobiol Aging 29(11):1733-43. [PubMed: 17513018]  [MGI Ref ID J:140908]

Austin MC; Schultzberg M; Abbott LC; Montpied P; Evers JR; Paul SM; Crawley JN. 1992. Expression of tyrosine hydroxylase in cerebellar Purkinje neurons of the mutant tottering and leaner mouse. Brain Res Mol Brain Res 15(3-4):227-40. [PubMed: 1279353]  [MGI Ref ID J:2495]

Ayata C; Shimizu-Sasamata M; Lo EH; Noebels JL; Moskowitz MA. 2000. Impaired neurotransmitter release and elevated threshold for cortical spreading depression in mice with mutations in the alpha1A subunit of P/Q type calcium channels Neuroscience 95(3):639-45. [PubMed: 10670432]  [MGI Ref ID J:60492]

Chou DKH; Jungalwala FB. 1996. N-Acetylglucosaminyl transferase regulates the expression of the sulfoglucuronyl glycolipids in specific cell types in cerebellum during development. J Biol Chem 271(46):28868-74. [PubMed: 8910533]  [MGI Ref ID J:37189]

Dove LS; Abbott LC; Griffith WH. 1998. Whole-cell and single-channel analysis of P-type calcium currents in cerebellar Purkinje cells of leaner mutant mice. J Neurosci 18(19):7687-99. [PubMed: 9742139]  [MGI Ref ID J:112100]

Dove LS; Nahm SS; Murchison D; Abbott LC; Griffith WH. 2000. Altered calcium homeostasis in cerebellar Purkinje cells of leaner mutant mice. J Neurophysiol 84(1):513-24. [PubMed: 10899223]  [MGI Ref ID J:103988]

Doyle J; Ren X; Lennon G; Stubbs L. 1997. Mutations in the Cacnl1a4 calcium channel gene are associated with seizures, cerebellar degeneration, and ataxia in tottering and leaner mutant mice. Mamm Genome 8(2):113-20. [PubMed: 9060410]  [MGI Ref ID J:38910]

Etheredge JA; Murchison D; Abbott LC; Griffith WH. 2007. Functional compensation by other voltage-gated Ca2+ channels in mouse basal forebrain neurons with Ca(V)2.1 mutations. Brain Res 1140:105-19. [PubMed: 16364258]  [MGI Ref ID J:120185]

Fletcher CF; Lutz CM; O'Sullivan TN; Shaughnessy JD Jr; Hawkes R; Frankel WN; Copeland NG; Jenkins NA. 1996. Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell 87(4):607-17. [PubMed: 8929530]  [MGI Ref ID J:36596]

Frank TC; Nunley MC; Sons HD; Ramon R; Abbott LC. 2003. Fluoro-jade identification of cerebellar granule cell and purkinje cell death in the alpha1A calcium ion channel mutant mouse, leaner. Neuroscience 118(3):667-80. [PubMed: 12710975]  [MGI Ref ID J:125604]

Frank-Cannon TC; Zeve DR; Abbott LC. 2007. Developmental expression of neuronal nitric oxide synthase in P/Q-type voltage-gated calcium ion channel mutant mice, leaner and tottering. Brain Res 1140:96-104. [PubMed: 16359645]  [MGI Ref ID J:120186]

Grusser-Cornehls U; Luy M; Baurle J. 1995. Electrophysiology and GABA-immunocytochemistry in the vestibular nuclei of normal (C57BL/6J) and Leaner mutant mice. Brain Res 703(1-2):51-62. [PubMed: 8719615]  [MGI Ref ID J:30260]

Heckroth JA; Abbott LC. 1994. Purkinje cell loss from alternating sagittal zones in the cerebellum of leaner mutant mice. Brain Res 658(1-2):93-104. [PubMed: 7834360]  [MGI Ref ID J:20921]

Herrup K; Wilczynski SL. 1982. Cerebellar cell degeneration in the leaner mutant mouse. Neuroscience 7(9):2185-96. [PubMed: 7145091]  [MGI Ref ID J:6909]

Hess EJ; Wilson MC. 1991. Tottering and leaner mutations perturb transient developmental expression of tyrosine hydroxylase in embryologically distinct Purkinje cells. Neuron 6(1):123-32. [PubMed: 1670919]  [MGI Ref ID J:10927]

Isaacs KR; Abbott LC. 1995. Cerebellar volume decreases in the tottering mouse are specific to the molecular layer. Brain Res Bull 36(3):309-14. [PubMed: 7697385]  [MGI Ref ID J:22482]

Isaacs KR; Abbott LC. 1992. Development of the paramedian lobule of the cerebellum in wild-type and tottering mice. Dev Neurosci 14(5-6):386-93. [PubMed: 1306163]  [MGI Ref ID J:14500]

Kaja S; van de Ven RC; Broos LA; Frants RR; Ferrari MD; van den Maagdenberg AM; Plomp JJ. 2007. Characterization of acetylcholine release and the compensatory contribution of non-Ca(v)2.1 channels at motor nerve terminals of leaner Ca(v)2.1-mutant mice. Neuroscience 144(4):1278-87. [PubMed: 17161543]  [MGI Ref ID J:121290]

Katoh A; Jindal JA; Raymond JL. 2007. Motor deficits in homozygous and heterozygous p/q-type calcium channel mutants. J Neurophysiol 97(2):1280-7. [PubMed: 17005620]  [MGI Ref ID J:135841]

Koyanagi Y; Sawada K; Sakata-Haga H; Jeong YG; Fukui Y. 2006. Increased serotonergic innervation of lumbosacral motoneurons of rolling mouse Nagoya in correlation with abnormal hindlimb extension. Anat Histol Embryol 35(6):387-92. [PubMed: 17156092]  [MGI Ref ID J:135940]

Lau FC; Abbott LC; Rhyu IJ; Kim DS; Chin H. 1998. Expression of calcium channel alpha1A mRNA and protein in the leaner mouse (tgla/tgla) cerebellum. Brain Res Mol Brain Res 59(1):93-9. [PubMed: 9729301]  [MGI Ref ID J:109328]

Lorenzon NM; Lutz CM; Frankel WN; Beam KG. 1998. Altered calcium channel currents in Purkinje cells of the neurological mutant mouse leaner. J Neurosci 18(12):4482-9. [PubMed: 9614225]  [MGI Ref ID J:47984]

Nahm SS; Frank TC; Browning MD; Sepulvado JM; Hiney JK; Abbott LC. 2003. Insulin-like growth factor-I improves cerebellar dysfunction but does not prevent cerebellar neurodegeneration in the calcium channel mutant mouse, leaner. Neurobiol Dis 14(2):157-65. [PubMed: 14572439]  [MGI Ref ID J:126207]

Nahm SS; Jung KY; Enger MK; Griffith WH; Abbott LC. 2005. Differential expression of T-type calcium channels in P/Q-type calcium channel mutant mice with ataxia and absence epilepsy. J Neurobiol 62(3):352-60. [PubMed: 15514988]  [MGI Ref ID J:116959]

Nahm SS; Tomlinson DJ; Abbott LC. 2002. Decreased calretinin expression in cerebellar granule cells in the leaner mouse. J Neurobiol 51(4):313-22. [PubMed: 12150506]  [MGI Ref ID J:116963]

Nair SM; Prasadarao N; Tobet SA; Jungalwala FB. 1993. Rostrocaudal expression of antibody HNK-1-reactive glycolipids in mouse cerebellum: relationship to developmental compartments and leaner mutation. J Comp Neurol 332(3):282-92. [PubMed: 8331216]  [MGI Ref ID J:12196]

Ogasawara M; Kurihara T; Hu Q; Tanabe T. 2001. Characterization of acute somatosensory pain transmission in P/Q-type Ca(2+) channel mutant mice, leaner. FEBS Lett 508(2):181-6. [PubMed: 11718712]  [MGI Ref ID J:72853]

Ovsepian SV; Friel DD. 2008. The leaner P/Q-type calcium channel mutation renders cerebellar Purkinje neurons hyper-excitable and eliminates Ca2+-Na+ spike bursts. Eur J Neurosci 27(1):93-103. [PubMed: 18093175]  [MGI Ref ID J:132196]

Rhyu IJ; Abbott LC; Walker DB; Sotelo C. 1999. An ultrastructural study of granule cell/Purkinje cell synapses in tottering (tg/tg), leaner (tg(la)/tg(la)) and compound heterozygous tottering/leaner (tg/tg(la)) mice. Neuroscience 90(3):717-28. [PubMed: 10218773]  [MGI Ref ID J:106598]

Rhyu IJ; Nahm SS; Hwang SJ; Kim H; Suh YS; Oda SI; Frank TC; Abbott LC. 2003. Altered neuronal nitric oxide synthase expression in the cerebellum of calcium channel mutant mice. Brain Res 977(2):129-40. [PubMed: 12834873]  [MGI Ref ID J:84467]

Sawada K; Haga H; Fukui Y. 2000. Ataxic mutant mice with defects in Ca2+ channel alpha-1A subunit gene: morphological and functional abnormalities in cerebellar cortical neurons Cong Anom 40:99-107.  [MGI Ref ID J:65744]

Sidman RL; Green MC; Appel DH. 1965. Tottering, tg, recessive, linkage group XVIII. In: Catalog of the Neurological Mutants of the Mouse. Harvard University Press.  [MGI Ref ID J:28459]

Southard JL. 1970. Leaner (la). Mouse News Lett 43:33.  [MGI Ref ID J:13510]

Tsuji S; Meier H. 1971. Evidence for allelism of leaner and tottering in the mouse. Genet Res 17(1):83-8. [PubMed: 4933322]  [MGI Ref ID J:5210]

Wakamori M; Yamazaki K; Matsunodaira H; Teramoto T; Tanaka I; Niidome T; Sawada K; Nishizawa Y; Sekiguchi N; Mori E; Mori Y; Imoto K. 1998. Single tottering mutations responsible for the neuropathic phenotype of the P-type calcium channel. J Biol Chem 273(52):34857-67. [PubMed: 9857013]  [MGI Ref ID J:51647]

Walter JT; Alvina K; Womack MD; Chevez C; Khodakhah K. 2006. Decreases in the precision of Purkinje cell pacemaking cause cerebellar dysfunction and ataxia. Nat Neurosci 9(3):389-97. [PubMed: 16474392]  [MGI Ref ID J:107094]

Xie G; Clapcote SJ; Nieman BJ; Tallerico T; Huang Y; Vukobradovic I; Cordes SP; Osborne LR; Rossant J; Sled JG; Henderson JT; Roder JC. 2007. Forward genetic screen of mouse reveals dominant missense mutation in the P/Q-type voltage-dependent calcium channel, CACNA1A Genes Brain Behav 6(8):717-27. [PubMed: 17376154]  [MGI Ref ID J:119639]

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]

Os related

Elliot SJ; Karl M; Berho M; Potier M; Zheng F; Leclercq B; Striker GE; Striker LJ. 2003. Estrogen deficiency accelerates progression of glomerulosclerosis in susceptible mice. Am J Pathol 162(5):1441-8. [PubMed: 12707027]  [MGI Ref ID J:83190]

Esposito C; He CJ; Striker GE; Zalups RK; Striker LJ. 1999. Nature and severity of the glomerular response to nephron reduction is strain-dependent in mice. Am J Pathol 154(3):891-7. [PubMed: 10079267]  [MGI Ref ID J:53353]

Falconer DS; Latyszewski M; Isaacson JH. 1964. Diabetes insipidus associated with oligosyndactylism in the mouse. Genet Res 5:473-488.  [MGI Ref ID J:12948]

Gruneberg H. 1956. Genetical studies on the skeleton of the mouse. XVIII. Three genes for syndactylism. J Genet 54:113-145.  [MGI Ref ID J:13049]

Gruneberg H. 1961. Genetical studies on the skeleton of the mouse. XXVII. The development of oligosyndactylism. Genet Res 2:33-42.  [MGI Ref ID J:12942]

He C; Esposito C; Phillips C; Zalups RK; Henderson DA; Striker GE; Striker LJ. 1996. Dissociation of glomerular hypertrophy, cell proliferation, and glomerulosclerosis in mouse strains heterozygous for a mutation (Os) which induces a 50% reduction in nephron number. J Clin Invest 97(5):1242-9. [PubMed: 8636436]  [MGI Ref ID J:32764]

He C; Zalups RK; Henderson DA; Striker GE; Striker LJ. 1995. Molecular analysis of spontaneous glomerulosclerosis in Os/+ mice, a model with reduced nephron mass. Am J Physiol 269(2 Pt 2):F266-73. [PubMed: 7544540]  [MGI Ref ID J:28323]

Jarad G; Lakhe-Reddy S; Blatnik J; Koepke M; Khan S; El-Meanawy MA; O'Connor AS; Sedor JR; Schelling JR. 2004. Renal phenotype is exacerbated in Os and lpr double mutant mice. Kidney Int 66(3):1029-35. [PubMed: 15327396]  [MGI Ref ID J:102341]

Kadam KM. 1962. Genetical studies on the skeleton of the mouse. XXXI. The muscular anatomy of syndactylism and oligosyndactylism. Genet Res 3:139-156.  [MGI Ref ID J:12944]

McLaren A. 1976. Genetics of the early mouse embryo. Annu Rev Genet 10:361-88. [PubMed: 797312]  [MGI Ref ID J:5768]

Milaire J. 1967. Histochemical observations on the developing foot of normal, oligosyndactylous (Os-plus) and syndactylous (sm-sm) mouse embryos. Arch Biol (Liege) 78(2):223-88. [PubMed: 4305644]  [MGI Ref ID J:5107]

Muhlfeld AS; Spencer MW; Hudkins KL; Kirk E; LeBoeuf RC; Alpers CE. 2004. Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice. Kidney Int 66(4):1393-402. [PubMed: 15458432]  [MGI Ref ID J:102315]

Naik DV; Valtin H. 1969. Hereditary vasopressin-resistant urinary concentrating defects in mice. Am J Physiol 217(4):1183-90. [PubMed: 5824320]  [MGI Ref ID J:5127]

Ovsepian SV; Friel DD. 2008. The leaner P/Q-type calcium channel mutation renders cerebellar Purkinje neurons hyper-excitable and eliminates Ca2+-Na+ spike bursts. Eur J Neurosci 27(1):93-103. [PubMed: 18093175]  [MGI Ref ID J:132196]

Pravtcheva DD; Wise TL. 2001. Disruption of Apc10/Doc1 in three alleles of oligosyndactylism. Genomics 72(1):78-87. [PubMed: 11247669]  [MGI Ref ID J:81567]

Sorenson CM; Rogers SA; Hammerman MR. 1996. Abnormal renal development in the Os/+ mouse is intrinsic to the kidney. Am J Physiol 271(1 Pt 2):F234-8. [PubMed: 8760267]  [MGI Ref ID J:34503]

Stewart AD; Stewart J. 1969. Studies on syndrome of diabetes insipidus associated with oligosyndactyly in mice. Am J Physiol 217(4):1191-8. [PubMed: 4309975]  [MGI Ref ID J:5128]

Van Valen P. 1966. Oligosyndactylism, an early embryonic lethal in the mouse. J Embryol Exp Morphol 15(2):119-24. [PubMed: 4289631]  [MGI Ref ID J:5017]

Wise TL; Pravtcheva DD. 2004. Oligosyndactylism mice have an inversion of chromosome 8. Genetics 168(4):2099-112. [PubMed: 15611179]  [MGI Ref ID J:95333]

Zalups RK. 1993. The Os/+ mouse: a genetic animal model of reduced renal mass. Am J Physiol 264(1 Pt 2):F53-60. [PubMed: 8430831]  [MGI Ref ID J:3842]

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
	Os +/+ ?
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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      JAX^® Mice Orders
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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

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.”

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.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

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.