Microphthalmia: A New Recessive Mutation in the Norway Rat

Moutier, R; Ostrowski, K.; Lamendin, H

doi:10.1093/oxfordjournals.jhered.a110798

Cited by 12 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animals. Animals used in this study were the offspring of ϩ / mib and mib / mib rats (originally derived from the stock of Dr. Rene Moutier, CNRS, Orleans, France [35] and generously donated by Dr. Sandy Marks, Jr., University of Massachusetts Medical School, Worcester, MA). The animals were bred and maintained at Harvard Medical School in accordance with Harvard guidelines.…”

Section: Methodsmentioning

confidence: 99%

“…In 1989, a spontaneous osteopetrotic mutation in the rat was described in which homozygotes display osteopetrosis at birth, but this defect in bone resorption dramatically improves with age ( 35 ). Because of associated small eyes and white coat color, the allele was called microphthalmia blanc ( mib ), although the nature of the mutation is to date unknown.…”

mentioning

confidence: 99%

“…The mib mutation is autosomal recessive, showing expression in homozygotes ( mib / mib ) with absence of skin and fur pigmentation, small eyes, and defects of incisor tooth eruption ( 36 ). The mib locus has previously been suggested to be different from microphthalmia ( mi ), incisorless ( ia ), osteopetrotic ( op ), or hypodactyly ( hd ) loci based on phenotypic differences and rough linkage estimates ( 35 ). Cielinski and Marks ( 37 , 38 ) have shown that the mib / mib mutant osteoclasts in newborn animals are decreased in number, do not form a ruffled border, and show decreased levels of mRNA for carbonic anhydrase II and tartrate-resistant ATPase.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Age-resolving Osteopetrosis: A Rat Model Implicating Microphthalmia and the Related Transcription Factor TFE3

Weilbaecher

Hershey

Takemoto

et al. 1998

The Journal of Experimental Medicine

View full text Add to dashboard Cite

Microphthalmia (Mi) is a basic helix-loop-helix–leucine zipper (b-HLH-ZIP) transcription factor implicated in pigmentation, mast cells, and bone development. Two dominant-negative mi alleles (mi/mi and Mior/Mior) in mice cause osteopetrosis. In contrast, osteopetrosis has not been observed in a number of recessive mi alleles, suggesting the existence of Mi protein partners important in osteoclast function. An osteopetrotic rat of unknown genetic defect (mib) has been described whose skeletal sclerosis improves dramatically with age and that is associated with pigmentation defects reminiscent of mouse mi alleles. Here we report that this rat strain harbors a large genomic deletion encompassing the 3′ half of mi including most of the b-HLH-ZIP region. Osteoclasts from these animals lack Mi protein in contrast to wild-type rat, mouse, and human osteoclasts. Mi is not detectable in primary osteoblasts. In addition TFE3, a b-HLH-ZIP transcription factor related to Mi, was found to be expressed in osteoclasts, but not osteoblasts, and to coimmunoprecipitate with Mi. These results demonstrate the existence of members of a family of biochemically related transcription factors that may cooperate to play a central role in osteoclast function and possibly in age-related osteoclast homeostasis.

show abstract

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Age-resolving Osteopetrosis: A Rat Model Implicating Microphthalmia and the Related Transcription Factor TFE3

Weilbaecher

Hershey

Takemoto

et al. 1998

The Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…However, based on the presence of certain functional domains, the subcellular localisation of the protein, and the osteoclast phenotypes of ia rats and the human patients, it likely plays a role in osteoclastic vesicular transport and ruffled border formation. A third osteopetrotic rat model is microphthalmia blanc ( mib ) [17], which has a mild and transient form of osteopetrosis due to a large deletion that truncates the encoded microphthalmia transcription factor [18]. The fourth and only remaining unknown, osteopetrotic mutation in the rat is osteopetrosis ( op ), first discovered by Moutier et al (1974) as a spontaneous, lethal mutation [1].…”

Section: Introductionmentioning

confidence: 99%

Refined Genomic Localization of the Genetic Lesion in the Osteopetrosis (op) Rat and Exclusion of Three Positional and Functional Candidate Genes, Clcn7, Atp6v0c, and Slc9a3r2

et al. 2009

View full text Add to dashboard Cite

Osteopetrosis is a disease characterised by a generalized skeletal sclerosis resulting from a reduced osteoclast-mediated bone resorption. Several spontaneous mutations lead to osteopetrotic phenotypes in animals. Moutier et al. (1974) discovered the osteopetrosis (op) rat as a spontaneous, lethal, autosomal recessive mutant. op rats have large non-functioning osteoclasts and severe osteopetrosis [1]. Dobbins et al. (2002) localised the disease causing gene to a 1.5 cM genetic interval on rat chromosome 10, which we confirm in the present report [2]. We also refined the genomic localisation of the disease gene and provide statistical evidence for a disease causing gene in a small region of rat chromosome 10. Three strong functional candidate genes are within the delineated region. Clcn7 was previously shown to underlie different forms of osteopetrosis, both in human and mice. ATP6v0c encodes a subunit of the vacuolar H(+)-ATPase or proton-pump. Mutations in TCIRG1, another subunit of the proton-pump, are known to cause a severe form of osteopetrosis. Given the critical role of proton pumping in bone resorption, the Slc9a3r2 gene, a sodium/hydrogen exchanger, was also considered as a candidate for the op mutation. RT-PCR showed that all 3 genes are expressed in osteoclasts, but sequencing found no mutations in either the coding regions nor in intron splice junctions. Our ongoing mutation analysis of other genes in the candidate region will lead to the discovery of a novel osteopetrosis gene and further insights into osteoclast functioning.

show abstract

“…The mib mutation in rats was discovered by Moutier, Ostrowski, and Lamendin in 1989. Characteristic features of this mutation include lack of pigmentation and skeletal sclerosis at birth, which diminishes during the 1st postnatal month.…”

Section: Introductionmentioning

confidence: 99%

Carbonic anhydrase II and H + -ATPase in osteoclasts of four osteopetrotic mutations in the rat

1999

Histochemistry and Cell Biology

View full text Add to dashboard Cite

Osteopetrosis in laboratory animals is a metabolic bone disease characterized by increased skeletal mass. It is inherited as an autosomal recessive and results from a defect in the development and/or function of osteoclasts. We studied two enzymes essential for bone resorption, carbonic anhydrase II isoenzyme (CA II) and H+ -ATPase, in osteoclasts from four osteopetrotic mutations in the rat; namely incisors-absent (ia), osteopetrosis (op), toothless (tl), and microphthalmia (mib), to test the hypothesis that reduced bone resorption in one or more of these mutations results from defects in the synthesis or activity of one of these enzymes. CA II was present in most osteoclasts from normal, tl, op, and mib littermates and was homogeneously distributed in cytoplasm. CA II staining in ia osteoclasts was more variable and less intense than in the other mutations. H+-ATPase was also present in osteoclasts from normal animals and mutants and immunostaining showed clear polarization to the ruffled border region in all normal rats and mutants except ia, which showed diffuse distribution of staining in the cytoplasm. H+-ATPase activity (proton transport) in a related tissue, kidney, was normal in tl and ia rats but increased in op and mib rats compared to their normal littermates. These results suggest that the osteoclasts in osteopetrotic rat mutations are not abnormal with respect to the distribution of CA II and H+ -ATPase and that the function of these enzymes in the skeleton, while likely normal, needs to be tested directly in bone.

show abstract

Microphthalmia: A New Recessive Mutation in the Norway Rat

Cited by 12 publications

References 0 publications

Age-resolving Osteopetrosis: A Rat Model Implicating Microphthalmia and the Related Transcription Factor TFE3

Age-resolving Osteopetrosis: A Rat Model Implicating Microphthalmia and the Related Transcription Factor TFE3

Refined Genomic Localization of the Genetic Lesion in the Osteopetrosis (op) Rat and Exclusion of Three Positional and Functional Candidate Genes, Clcn7, Atp6v0c, and Slc9a3r2

Carbonic anhydrase II and H + -ATPase in osteoclasts of four osteopetrotic mutations in the rat

Contact Info

Product

Resources

About