Description

Strain Information

Type Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse

Appearance
agouti, ataxic, tremors
Related Genotype: A/A Lpin1^fld-2J/Lpin1^fld-2J

agouti, unaffected
Related Genotype: A/A Lpin1^fld-2J/+

Description
Homozygous fatty liver dystrophy (fld) mice have an enlarged, fatty liver and hypertriglyceridemia which resolve to normal during the weaning transition. However, decreased overall size, decreased lipid in the fat pads, and a peripheral neuropathy persist throughout the lifespan. This peripheral neuropathy manifests as a tremor and an unsteady gait shortly after 10 days of age and worsens with age. The fld neuropathy is specific to the peripheral nervous system. Electron microscopy of sciatic nerves revealed thin, poorly compacted myelin sheaths, hypertrophic Schwann cells, myelin debris, degenerating axons, bands of Bugner, and regenerative clusters, but no evidence of inflammation (Langner et al, 1991). Western blot analysis of sciatic nerve from two-to-three month old fld/fld mice showed a 7-13-fold reduction in myelin P₀, a vast increase in apoE, an increase in GAP-43, and no detectable myelin P₂. It was also noted that an antibody to neurofilament 68K detected bands of lower molecular mass in the fld/fld sciatic nerve extracts than in wild-type, suggesting degradation of neurofilament 68K. Furthermore, TLC of fld/fld sciatic nerve lipids revealed decreased levels of phospholipids, glycosphingolipids, and some neutral lipids and increased levels of cholesterol esters. These combined findings support the postulate put forward by Langner et al. that fld/fld peripheral neuropathy involves "dysmyelination and concomitant demyelination" (Langner et al., 1991). In light of the role of insulin in Schwann cell and adipocyte differentiation and metabolism, it is noteworthy that fld/fld mice have been found to have altered insulin responsiveness (Klingenspor et al., 1999).

The fld critical region was fine-mapped to a 0.42 cM interval on chromosome 12. RT-PCR of liver extracts from 6- and 21-day-old pups revealed an absence in fld/fld liver of transcript from one of the genes in this interval, formerly called Kiaa0188, now known to be the gene encoding lipin. (Peterfy et al. 1999; Peterfy et al. 2001)

fld^2J is a spontaneous point mutation in Lpin1 which occurred on C3H/HeJ in 1994. An unstable gait and tremor by 3 weeks of age was initially observed. An allele test with the original fld mutation was positive. Histological examination shows peripheral neuropathy. The pups have a fatty liver before reaching wean age. As with the original mutation of fld, homozygous femal es will breed and raise their litters. Homozygous males have not been bred.

Development
This spontaneous mutation occurred on C3H/HeJ at The Jackson Laboratory in 1994. It was bred twice by ovarian transplant crossed with a C3FeLe.B6-a male, and has been maintained by sibling mating since then. No non-agouti has been introduced since those early crosses to C3FeLe.B6-a and no black mice have seen in this colony since March, 1995. (1/25/01 MB).

Control Information

	Control
	Heterozygote from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Lpin1

002533	B6 x BALB/cByJ-Lpin1fld/J
001592	BALB/cByJ-Lpin1fld/J

View Strains carrying other alleles of Lpin1     (2 strains)

Phenotype

Phenotype Information

View Research Applications

Research Applications

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

Lpin1^fld-2J related

Cardiovascular Research
Hypertriglyceridemia

Dermatology Research
Skin and Hair Texture Defects

Developmental Biology Research
Growth Defects
Internal/Organ Defects (liver)
Neurodevelopmental Defects
Postnatal Mortality

Diabetes and Obesity Research
Hyperinsulinemia (moderate)
Impaired Insulin Processing
Insulin Resistance

Endocrine Deficiency Research
Adipose Defects

Internal/Organ Research
Adipose Defects
Liver Defects

Metabolism Research
Lipid Metabolism

Neurobiology Research
Ataxia (Movement) Defects
Metabolic Defects
Myelination Defects (peripheral neuropathy)
Neurodegeneration
Neurodevelopmental Defects
Tremor Defects

Reproductive Biology Research
Fertility Defects

Currently there is no phenotype information for this strain.

Genes & Alleles

Gene & Allele Information

Allele Symbol		Lpin1fld-2J
Allele Name		fatty liver dystrophy 2 Jackson
Allele Type		Spontaneous
Common Name(s)		fld2J;
Strain of Origin		C3H/HeJ
Gene Symbol and Name		Lpin1, lipin 1
Chromosome		12
Gene Common Name(s)		DKFZp781P1796; KIAA0188; PAP1; fatty liver dystrophy; fld; mKIAA0188;
General Note		This remutation arose at the Jackson Laboratory in 1998, and was found to be an allele of Lpin1fld. Heterozygotes for the new mutation and for Lpin1fld produced 6 affected mice of 10 born. PCR for markers on chromosome 12 further confirmed the allelism test. Similar to the original Lpin1fld mutant mouse, affected newborns have an enlarged liver that normalizes by weaning. Homozygotes develop an unsteady gait and tremor by three weeks of age. Female homozygotes breed, but homozygous males have not been bred. Pathological examination of liver from newborns revealed fatty infiltration as in the original fld mutation and peripheral neuropathy was found in affected mice from four weeks onward (J:51014, J:51188).
Molecular Note		A G-to-A transition mutation in codon 84 is predicted to alter this residue from a glycine to an arginine in the encoded protein. This position corresponds to the NLIP domain of the protein and is highly conserved in other species. [MGI Ref ID J:66739]

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

Klingenspor M; Xu P; Cohen RD; Welch C; Reue K. 1999. Altered gene expression pattern in the fatty liver dystrophy mouse reveals impaired insulin-mediated cytoskeleton dynamics. J Biol Chem 274(33):23078-84. [PubMed: 10438476]  [MGI Ref ID J:42314]

Langner CA; Birkenmeier EH; Ben-Zeev O; Schotz MC; Sweet HO; Davisson MT; Gordon JI. 1989. The fatty liver dystrophy (fld) mutation. A new mutant mouse with a developmental abnormality in triglyceride metabolism and associated tissue-specific defects in lipoprotein lipase and hepatic lipase activities. J Biol Chem 264(14):7994-8003. [PubMed: 2722772]  [MGI Ref ID J:9801]

Langner CA; Birkenmeier EH; Roth KA; Bronson RT; Gordon JI. 1991. Characterization of the peripheral neuropathy in neonatal and adult mice that are homozygous for the fatty liver dystrophy (fld) mutation. J Biol Chem 266(18):11955-64. [PubMed: 2050689]  [MGI Ref ID J:82882]

Peterfy M; Phan J; Xu P; Reue K. 2001. Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin Nat Genet 27(1):121-4. [PubMed: 11138012]  [MGI Ref ID J:66739]

Rehnmark S; Giometti CS; Slavin BG; Doolittle MH; Reue K. 1998. The fatty liver dystrophy mutant mouse: microvesicular steatosis associated with altered expression levels of peroxisome proliferator-regulated proteins. J Lipid Res 39(11):2209-17. [PubMed: 9799807]  [MGI Ref ID J:50756]

Reue K; Doolittle MH. 1996. Naturally occurring mutations in mice affecting lipid transport and metabolism. J Lipid Res 37(7):1387-405. [PubMed: 8827513]  [MGI Ref ID J:34179]

Reue K; Xu P; Wang XP; Slavin BG. 2000. Adipose tissue deficiency, glucose intolerance, and increased atherosclerosis result from mutation in the mouse fatty liver dystrophy (fld) gene J Lipid Res 41(7):1067-76. [PubMed: 10884287]  [MGI Ref ID J:63448]

Lpin1^fld-2J related

Donahue LR. 1999. The Jackson Laboratory Mouse Mutant Resource 1999 Mutation Reports MGI Direct Data Submission :.  [MGI Ref ID J:51014]

Peterfy M; Phan J; Xu P; Reue K. 2001. Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin Nat Genet 27(1):121-4. [PubMed: 11138012]  [MGI Ref ID J:66739]

Samples R. 1999. The Jackson Laboratory Mouse Mutant Resource 1999 Mutation Reports MGI Direct Data Submission :.  [MGI Ref ID J:51188]

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 of Strains Needing Progeny Testing. 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 untested males and two untested females (two pairs) will be recovered, 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 overall recovery time to approximately 25 weeks. However, all pups recovered will be sent. Progeny testing is required to identify the genotype of mice of this strain, as a genotyping assay is not available. This type of testing involves breeding the recovered animals and assessing the phenotype of the offspring in order to identify animals carrying the mutation of interest. We can perform the progeny testing for you as a service or we can ship all recovered animals (at least two untested pairs) to you for progeny testing at your facility. If you perform the progeny testing, there is NO guarantee that a carrier will be identified. If we perform progeny testing as a service, additional breeding time will be required. In this case, when a male and female (one pair) are identified that carry the mutation, they and their offspring will be shipped. Delivery time for strains requiring progeny testing often exceeds 25 weeks and may take 12 months or more due to the difficulties in breeding some strains. The progeny testing cost is in addition to the recovery cost and is based on the number of boxes used and the time taken to produce the mice identified as carrying the mutation. Please note that identified 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. Please contact Customer Service for more information on the cost of progeny testing for a strain: Tel: 1-800-422-6423 or 1-207-288-5845. 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

	Control
	Heterozygote 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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Ordering and Purchasing Information

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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

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