Strain Name:

C57BL/6J-Slc30a4lm/J

Stock Number:

000219

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Availability:

Cryopreserved - Ready for recovery

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Strain; Spontaneous Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse

Appearance
black
Related Genotype: a/a

Description
Female mice homozygous for the lethal milk mutation (Slc30a4lm, formerly Znt4lm) produce milk that is lethal to mice nursed during the first week of life and detrimental to mice nursed thereafter. The lethal and detrimental effects are due to a deficiency of zinc in the milk. If foster nursed on normal dams, lethal milk homozygotes survive and become reproductively mature. Zinc supplementation of the drinking water of dams enables them to nurse their young successfully. All homozygous mutant mice lack utricular otoliths and this defect is not prevented by zinc supplementation. They have varying loss of saccular otoliths and show mild behavioral abnormalities related to the otolith defect. Homozygotes over eight months of age show progressive hair loss, dermatitis, and skin lesions, symptoms of zinc deficiency.

Development
Lethal milk (lm) arose spontaneously at The Jackson Laboratory in 1964 in the C57BL/6J inbred strain. The strain has been maintained homozygous through sibling breeding. Because homozygous pups die by 5 to 8 days of age due to the zinc deficiency in the homozygous mother's milk, they are foster nursed. In 1983 embryos were cryopreserved from matings of C57BL/6J females with homozygous males at generation F54.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Slc30a4lm/Slc30a4lm

        C57BL/6J-Slc30a4lm
  • mortality/aging
  • partial postnatal lethality
    • pups nursed on lethal milk produced by mutant dams die prior to weaning; however, pups develop normally if fostered on wild-type dams   (MGI Ref ID J:5911)
    • all newborn pups succumb to death after 3 days of nursing on lethal milk, even after subsequent transfer to a wild-type dam; however, mutant pups survive if foster-nursed before 3 days of age to a wild-type dam   (MGI Ref ID J:5911)
    • 40% survive to weaning age   (MGI Ref ID J:7690)
    • lethality of sucklings can be prevented by supplementing drinking water of dams with zinc   (MGI Ref ID J:7690)
  • behavior/neurological phenotype
  • abnormal behavior
    • pups, if disturbed in the nest, have a propensity to remain on their backs   (MGI Ref ID J:7690)
    • impaired righting response
      • delay in righting response   (MGI Ref ID J:7690)
    • impaired swimming
      • mice show variable ability to swim   (MGI Ref ID J:89392)
      • mice are completely disoriented when swimming and maintain an unusual vertical position, keeping the nose barely out of the water   (MGI Ref ID J:7690)
    • stereotypic behavior
      • older mice show a 'tail spinning' behavior when held by the tail   (MGI Ref ID J:7690)
  • hearing/vestibular/ear phenotype
  • abnormal linear vestibular evoked potential
    • variable defects in latencies, amplitudes and thresholds of VESPs, dependent on amounts of otoconia present   (MGI Ref ID J:89392)
    • absent linear vestibular evoked potential
      • mice with absent otoconia show absent vestibular compound action potentials   (MGI Ref ID J:89392)
  • abnormal otolith morphology
    • absence of utricular otoconia   (MGI Ref ID J:7690)
    • saccular, but not utricular, otolith defect is alleviated by zinc supplementation of the dam   (MGI Ref ID J:7690)
    • mice show variable losses of saccular otoconia   (MGI Ref ID J:89392)
    • gigantic crystals are seen in the saccule   (MGI Ref ID J:7690)
  • immune system phenotype
  • dermatitis
    • exhibited in mice after 8 months   (MGI Ref ID J:7690)
    • 8-day-old pups nursed on lethal milk show focal acute dermatitis   (MGI Ref ID J:5911)
  • endocrine/exocrine gland phenotype
  • abnormal lactation
    • mutant dams frequently produce less milk than wild-type dams   (MGI Ref ID J:5911)
    • abnormal milk composition
      • dams produce zinc-deficient milk that is lethal to all nursing pups   (MGI Ref ID J:7690)
      • mutant females produce milk that is lethal to the offspring at 5-8 days of age; however, the fat and protein components appear to be normal and no differences in fatty acid or in vitamin A and D content are observed   (MGI Ref ID J:30724)
      • mutant lactating dams produce lethal milk that contains 34% less zinc than that of wild-type dams; however, copper, calcium, iron, and magnesium levels remain normal   (MGI Ref ID J:5911)
  • abnormal mammary gland growth during lactation
    • the mammary glands of mutant lactating dams are generally smaller (and less active) than wild-type   (MGI Ref ID J:5911)
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • no aberrant bleeding time after tail vein nick   (MGI Ref ID J:29151)
    • abnormal zinc homeostasis
      • 8-day-old pups suckling on lethal milk show a 34% reduction in whole body zinc concentration; however, no zinc deficiency is observed in the plasma of nursing pups or lactating dams or in adult female carcasses   (MGI Ref ID J:5911)
      • unlike wild-type dams where the zinc concentration in milk is 10-fold higher than that in plasma, mutant dams show only a 3-fold higher concentration in milk, suggesting impaired zinc transport from plasma to milk   (MGI Ref ID J:5911)
      • develop systemic zinc deficiency by 8 months of age   (MGI Ref ID J:7690)
  • other phenotype
  • maternal effect
    • mutant females produce milk that is lethal to their progeny: offspring appears to swell, shrivel and dry up, joints stiffen, mouths remain open, and death occurs at around 6 to 8 days of age   (MGI Ref ID J:30724)
    • if 5-day old offspring are foster-nursed on wild-type females they do not survive; however, if offspring are fostered at 0 to 2 days of age most survive and reach reproductive maturity   (MGI Ref ID J:30724)
    • if wild-type 5- or 7-day old litters are fostered on mutant females, most pups survive but tend to be smaller at weaning; however, if wild-type newborns are fostered on mutant females, they die at 6-8 days of life   (MGI Ref ID J:30724)
    • mutant lactating dams produce zinc-deficient milk that is lethal to all nursing pups; however, mutant pups develop normally is foster-nursed on a wild-type dam   (MGI Ref ID J:5911)
    • i.p. injection of zinc glycinate into nursing pups significantly improves survival, with 70% of pups surviving on lethal milk to 16 days of age with nearly normal body weights; 80% of these survivors display normal pelage   (MGI Ref ID J:5911)
    • i.p. injection of glycine into nursing pups enhances survival by 30% but fails to correct the fur and weight loss phenotypes   (MGI Ref ID J:5911)
    • i.p. injection of copper glycinate fails to ameliorate the adverse effects of toxic milk   (MGI Ref ID J:5911)
  • growth/size phenotype
  • decreased body weight   (MGI Ref ID J:7690)
  • postnatal growth retardation
    • all pups nursed on lethal milk display stunted growth   (MGI Ref ID J:5911)
  • pigmentation phenotype
  • abnormal coat/hair pigmentation
    • portions of the normal black, nonagouti hair often shows a bronzing effect, becoming reddish in patches   (MGI Ref ID J:7690)
  • vision/eye phenotype
  • cataracts
    • lens opacity   (MGI Ref ID J:7690)
  • corneal opacity   (MGI Ref ID J:7690)
  • integument phenotype
  • abnormal coat/hair pigmentation
    • portions of the normal black, nonagouti hair often shows a bronzing effect, becoming reddish in patches   (MGI Ref ID J:7690)
  • abnormal hair shaft morphology
    • 8-day-old pups nursed on lethal milk display a significantly reduced number of hair shafts   (MGI Ref ID J:5911)
  • abnormal lactation
    • mutant dams frequently produce less milk than wild-type dams   (MGI Ref ID J:5911)
    • abnormal milk composition
      • dams produce zinc-deficient milk that is lethal to all nursing pups   (MGI Ref ID J:7690)
      • mutant females produce milk that is lethal to the offspring at 5-8 days of age; however, the fat and protein components appear to be normal and no differences in fatty acid or in vitamin A and D content are observed   (MGI Ref ID J:30724)
      • mutant lactating dams produce lethal milk that contains 34% less zinc than that of wild-type dams; however, copper, calcium, iron, and magnesium levels remain normal   (MGI Ref ID J:5911)
  • abnormal mammary gland growth during lactation
    • the mammary glands of mutant lactating dams are generally smaller (and less active) than wild-type   (MGI Ref ID J:5911)
  • alopecia
    • sparse hair behind the pinnae and over the shoulders by 8 months of age, followed by more extensive hair loss over the body and head   (MGI Ref ID J:7690)
    • all pups nursed on lethal milk exhibit alopecia   (MGI Ref ID J:5911)
  • dermatitis
    • exhibited in mice after 8 months   (MGI Ref ID J:7690)
    • 8-day-old pups nursed on lethal milk show focal acute dermatitis   (MGI Ref ID J:5911)
  • hair follicle degeneration
    • 8-day-old pups nursed on lethal milk display follicular atrophy   (MGI Ref ID J:5911)
  • skin lesions
    • exhibited in mice after 8 months   (MGI Ref ID J:7690)
  • thick epidermis stratum granulosum
    • 8-day-old pups nursed on lethal milk exhibit a thickened stratum granulosum   (MGI Ref ID J:5911)
View Research Applications

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

Slc30a4lm related

Dermatology Research
Skin and Hair Texture Defects

Developmental Biology Research
Growth Defects

Metabolism Research

Neurobiology Research
Hearing Defects
Metabolic Defects

Sensorineural Research
Hearing Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Slc30a4lm
Allele Name lethal milk
Allele Type Spontaneous
Common Name(s) lm;
Strain of OriginC57BL/6J
Gene Symbol and Name Slc30a4, solute carrier family 30 (zinc transporter), member 4
Chromosome 2
Gene Common Name(s) ZNT4; Znt4; lethal milk; lm; zinc transporter 4;
Molecular Note The mutation in the lethal milk mouse is a C-to-T substitution at position 934, resulting in an arginine to a stop codon at position 297 of the encoded protein. [MGI Ref ID J:43841]

Genotyping

Genotyping Information

Genotyping Protocols

Slc30a4lm, End Point Analysis
Slc30a4lm, Restriction Enzyme Digest


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Erway LC; Grider A Jr. 1984. Zinc metabolism in lethal-milk mice. Otolith, lactation, and aging effects. J Hered 75(6):480-4. [PubMed: 6512240]  [MGI Ref ID J:7690]

Jones SM; Erway LC; Johnson KR; Yu H; Jones TA. 2004. Gravity receptor function in mice with graded otoconial deficiencies. Hear Res 191(1-2):34-40. [PubMed: 15109702]  [MGI Ref ID J:89392]

Piletz JE; Ganschow RE. 1978. Zinc deficiency in murine milk underlies expression of the lethal milk (lm) mutation. Science 199(4325):181-3. [PubMed: 619449]  [MGI Ref ID J:5911]

Slc30a4lm related

Ackland ML; Mercer JF. 1992. The murine mutation, lethal milk, results in production of zinc-deficient milk. J Nutr 122(6):1214-8. [PubMed: 1588438]  [MGI Ref ID J:2205]

Dickie MM. 1969. lm Mouse News Lett 41:30-1.  [MGI Ref ID J:30724]

Erway LC; Grider A Jr. 1984. Zinc metabolism in lethal-milk mice. Otolith, lactation, and aging effects. J Hered 75(6):480-4. [PubMed: 6512240]  [MGI Ref ID J:7690]

Huang L; Gitschier J. 1997. A novel gene involved in zinc transport is deficient in the lethal milk mouse. Nat Genet 17(3):292-7. [PubMed: 9354792]  [MGI Ref ID J:43841]

Jones SM; Erway LC; Johnson KR; Yu H; Jones TA. 2004. Gravity receptor function in mice with graded otoconial deficiencies. Hear Res 191(1-2):34-40. [PubMed: 15109702]  [MGI Ref ID J:89392]

Lee DY; Prasad AS; Brewer GJ. 1993. Neonatal zinc deficiency in pups nursing on lethal milk dams J Trace Elem Exp Med 6(2):45-52.  [MGI Ref ID J:15160]

Lee DY; Shay NF; Cousins RJ. 1992. Altered zinc metabolism occurs in murine lethal milk syndrome. J Nutr 122(11):2233-8. [PubMed: 1432264]  [MGI Ref ID J:3620]

Piletz JE; Ganschow RE. 1978. Zinc deficiency in murine milk underlies expression of the lethal milk (lm) mutation. Science 199(4325):181-3. [PubMed: 619449]  [MGI Ref ID J:5911]

Piletz JE; Herschman HR. 1982. Induction of metallothionein by zinc in lethal milk mutant mice. Biochem Genet 20(11-12):1221-33. [PubMed: 7165696]  [MGI Ref ID J:7002]

Sundberg JP (ed.). 1994. Handbook of Mouse Mutations with Skin and Hair Abnormalities: Animal Models and Biomedical Tools. In: Handbook of Mouse Mutations with Skin and Hair Abnormalities: Animal Models and Biomedical Tools. CRC Press, Boca Raton.  [MGI Ref ID J:30359]

Swank RT; Reddington M; Howlett O; Novak EK. 1991. Platelet storage pool deficiency associated with inherited abnormalities of the inner ear in the mouse pigment mutants muted and mocha. Blood 78(8):2036-44. [PubMed: 1912584]  [MGI Ref ID J:29151]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2250.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of 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 about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2925.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of 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 about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

General Supply Notes

  • View the complete collection of spontaneous mutants in the Mouse Mutant Resource.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Important Note

Litters born to homozygous females should be fostered. Stock No. 003550 B6EiD2F1/J are recommended as foster mothers for this strain.

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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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