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PubMed1995

The BALB/c mouse B-cell response to pigeon cytochrome c initiates as a heteroclitic response specific for the self antigen mouse cytochrome c.

Direct evidence is presented in support of the longstanding but unproven hypothesis that B lymphocytes specific for self antigens (Ags) can be used in the immune response to foreign Ags. We show that the B cells in BALB/c mic responding early to pigeon cytochrome c (CYT) produce antibodies that recognize and bind the major antigenic site on mouse CYT with greater affinity than they bind pigeon CYT i.e., they are heteroclitic for the self Ag. Furthermore, these B cells express the same combination of immunoglobulin variable region (V) genes that are known to be used in B-cell recognition of mouse CYT. Over time, the response to pigeon CYT becomes more specific for the foreign Ag through the recruitment of B cells expressing different combinations of V genes and, possibly, somatic mutation of the mouse CYT specific B cells from early in the response. Cross-recognition of pigeon CYT by mouse CYT-specific B cells results from the sharing of critical amino acid residues by the two Ags. Although B-cell recognition of the self Ag, mouse CYT, is very specific, which limits the extent to which foreign Ags can cross-activate the autoreactive B cells, it is possible that polyreactive B cells to other self Ags may be used more frequently in response to foreign Ags.

Amino Acid Sequence↗
PubMed1992

Reactivation of a major histocompatibility complex class II gene in mouse plasmacytoma cells and mouse T cells.

Terminally differentiated plasma cells and mouse T cells do not express major histocompatibility complex (MHC) class II genes although class II gene expression is observed in pre-B and mature B cells as well as in activated human T cells. Transient heterokaryons were prepared and analyzed to investigate the mechanisms of inactivation of MHC class II gene in mouse plasmacytoma cells and mouse T cells. The endogenous MHC class II genes in both mouse plasmacytoma cells and mouse T cells can be reactivated by factors present in B cells. This reactivation of class II gene is also observed by fusion with a human T cell line which expresses MHC class II genes, but not with a class II negative human T cell line. It appears that the loss of MHC class II gene expression during the terminal differentiation of B cells or T cell lineage is due to absence of positive regulatory factor(s) necessary for class II transcription.

Animals↗
PubMed1989

Hydrolysis of bisphenol A diglycidylether by epoxide hydrolases in cytosolic and microsomal fractions of mouse liver and skin: inhibition by bis epoxycyclopentylether and the effects upon the covalent binding to mouse skin DNA.

Synergistic interactions have been reported in the carcinogenicity of two epoxy resin components to mouse skin. A mixture of bisphenol A diglycidylether and bis epoxycyclopentylether was highly carcinogenic, despite the fact that neither compound gave positive results when applied individually. To elucidate the mechanism of this synergistic interaction we have investigated the effects of bis epoxycyclopentylether upon the hydrolysis and DNA-binding of bisphenol A diglycidylether. This glycidylether was rapidly hydrolysed by microsomal and cytosolic fractions of mouse liver and skin. In three different mouse strains the specific epoxide hydrolase activities were 28.3-48.5; 33.0-38.8; 7.9-10.2 and 0.85-0.98 nmol/mg protein/min for liver microsomal and cytosolic and skin microsomal and cytosolic fractions respectively. This is the first demonstration of an epoxide hydrolase activity in skin cytosolic fractions. Bis epoxycyclopentylether inhibited the microsomal activities. This inhibition appeared to be slightly more effective with microsomal fractions from liver. The effect of this inhibition upon the binding of bisphenol A diglycidylether to mouse skin DNA was investigated using bisphenol A diglycidylether radiolabelled at two different positions. When high doses of bisphenol A diglycidylether were applied to the mouse skin one major DNA adduct was observed which was identified as a glycidaldehyde adduct. This adduct was not detectable at the lowest bisphenol A diglycidylether dose tested, unless bis epoxycyclopentylether was applied simultaneously. These findings suggest that glycidaldehyde may be formed from bisphenol A diglycidylether. At low doses, however, the epoxide groups are hydrolysed before glycidaldehyde can be formed, unless the epoxide hydrolase is inhibited. Such inhibition and the associated increased production of glycidaldehyde may account for the potentiation of the carcinogenic response in the epoxide mixture.

Animals↗
PubMed1985

Effect of ellagic acid and hydroxylated flavonoids on the tumorigenicity of benzo[a]pyrene and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene on mouse skin and in the newborn mouse.

Ellagic acid, quercetin and robinetin were tested for their ability to antagonize the tumor-initiating activity of benzo[a]pyrene (B[a]P) and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the ultimate carcinogenic metabolite of benzo[a]-pyrene. Ellagic acid, robinetin or quercetin (2500 nmol) had no tumor-initiating activity on mouse skin, but the topical application of 2500 nmol of ellagic acid 5 min before a tumor-initiating dose of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2 caused a 59-66% inhibition in the number of skin tumors per mouse that were observed after 15-20 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate. Similar treatment with 2500 nmol of robinetin or quercetin caused a statistically insignificant 16-24% inhibition in the tumor-initiating activity of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2 applied 5 min later. Treatment of mice with 2500 nmol of ellagic acid 5 min before the application of 50 nmol of B[a]P inhibited the mean number of skin tumors per mouse by 28-33% after 15-20 weeks of promotion, but these decreases were not statistically significant. Robinetin and quercetin had little or no effect on the tumor-initiating activity of B[a]P on mouse skin. Treatment of preweanling mice with 1/7, 2/7 and 4/7 of the total dose of ellagic acid (300 nmol), robinetin (1400 nmol), myricetin (1400 nmol) or quercetin (1400 nmol) i.p. on their first, eighth and fifteenth day of life, respectively, did not cause the formation of tumors in animals that were killed 9-11 months later. Similar treatment of preweanling mice with the above doses of the phenolic compounds 10 min before the i.p. injection of a total dose of 30 nmol of B[a]P 7,8-diol-9,10-epoxide-2 during the animal's first 15 days of life caused a 44-75% inhibition in the number of diol-epoxide-induced pulmonary tumors per mouse. Similar treatment with these plant phenols had little or no effect on B[a]P-induced pulmonary tumors.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2004

Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries.

We have been conducting a mouse cDNA project to predict protein-coding sequences of mouse homologues of human KIAA and FLJ genes since 2001. As an extension of these projects, we herein present the entire sequences of 500 mKIAA cDNA clones and 4 novel cDNA clones that were incidentally identified during this project. We have isolated cDNA clones from the size-fractionated mouse cDNA libraries derived from 7 tissues and 3 types of cultured cells. The average size of the 504 cDNA sequences reached 4.3 kb and that of the deduced amino acid sequences from these cDNAs was 807 amino acid residues. We assigned the integrity of CDSs from the comparison with the corresponding human KIAA cDNA sequences. The comparison of mouse and human sequences revealed that two different human KIAA cDNAs are derived from single genes. Furthermore, 3 out of 4 proteins encoded in the novel cDNA clones showed moderate sequence similarity with human KIAA proteins, thus we could obtain new members of KIAA protein families through our mouse cDNA projects.

Animals↗
PubMed2005

Characterization of the structure and expression of mouse Itpa gene and its related sequences in the mouse genome.

In the mouse genome, we found one processed Itpa gene-like sequence and two processed Itpa pseudogenes as well as the Itpa gene itself with introns, located on chromosome 2F3, which was isolated by a retro-recombination method. We also identified three types (A, B, C) of Itpa transcripts in mouse tissues. The processed Itpa gene-like sequence located on chromosome 2E1 has a complete open reading frame for exactly the same polypeptide as ITPA encoded by the type A transcript, with a polyadenylation signal. However, no transcribed sequence derived from the Itpa gene-like sequence was detectable in any of the mouse tissues examined, thus naming the sequence as Itpa processed pseudogene alpha. The type A Itpa mRNA, which was expressed in all mouse tissues examined, only encodes mouse ITPA polypeptide consisting of 198 amino acid residues with a capacity to hydrolyze dITP into dIMP. Itpa mRNA was detected in all tissues examined, and its expression is especially high in the testis, brain, and thymus. ITPA protein was mostly detected in the cytoplasm, to a lesser extent in the nuclei of neurons in the brain, and also those of hepatocytes, epithelial cells lining the bile duct, and endothelial cells lining the portal vein in the liver.

Alternative Splicing↗
PubMed1994

Detection of hydroquinone-induced nonrandom breakage in the centromeric heterochromatin of mouse bone marrow cells using multicolor fluorescence in situ hybridization with the mouse major and minor satellite probes.

Fluorescence in situ hybridization with a mouse major satellite probe and CREST staining were used to characterize the origin of micronuclei occurring in mouse bone marrow erythrocytes following administration of the benzene metabolite hydroquinone. Hydroquinone was administered to male CD-1 mice by i.p. injection on three consecutive days and the bone marrow cells were harvested 24 h later. A pronounced difference in the results was observed using the two approaches: 63% of the micronuclei induced by hydroquinone labeled with the major satellite probe whereas only 28% labeled with the CREST antibody. To determine whether the observed difference was due to a disruption of the kinetochore or a result of breakage within centromeric heterochromatin, we developed a tandem label multicolor hybridization assay, which requires the presence of both the mouse major and minor satellite probes in a micronucleus for a classification of chromosomal loss. The minor probe targets a centromeric region physically linked to the short arm of mouse chromosomes, whereas the major probe hybridizes to the centromeric heterochromatin adjacent to the long arm. Using this approach, 29% of the micronuclei induced by hydroquinone hybridized with both the major and minor satellite probes, indicating chromosome loss; an additional 37% labeled with only the major satellite probe indicating breakage within the centromeric heterochromatin. Although the region targeted by the major satellite probe comprises only 5-10% of the mouse genome, these major-probe containing micronuclei represent 53% of the micronuclei formed as the result of chromosome breakage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Mouse DNA polymerase beta gene promoter: fine mapping and involvement of Sp1-like mouse transcription factor in its function.

The promoter of mouse DNA polymerase beta gene was analyzed by combining 5'-upstream region of this gene with chloramphenicol acetyltransferase (CAT) gene and by introduction of the recombinant plasmid DNA into mouse NIH/3T3 cells. Serial deletion of the mouse DNA sequence revealed that the promoter function resides within a 33 base pair region from the nucleotide position -48 to -15 with respect to the transcription initiation site, and is highly active without enhancer sequence. The promoter region was separated into two subregions: one (-48 to -35) contains a GC-box and the other contains a 10 base pair palindrome, whose sequence is similar to one of promoter consensus sequences found in a number of promoters including adenovirus promoters. The DNA polymerase beta promoter-directed CAT expression was competitively inhibited by the simultaneous transfection of plasmid DNA containing SV40 early promoter sequence. The viral sequences which are competitive to the GC-box of DNA polymerase beta gene promoter were the GC-boxes of SV40 promoter. Therefore, it is concluded that transcription of mouse DNA polymerase beta gene is regulated by mouse trans-acting factors equivalent to human Sp1 which is known to be trans-acting protein factor acting on SV40 GC-box sequences.

Animals↗
PubMed1979

Methylation of DNA in mouse early embryos, teratocarcinoma cells and adult tissues of mouse and rabbit.

The distribution and amount of 5-methylcytosine (5-MeCyt) in DNA was measured for early embryos of mouse strain CF1 (2 to 4 cell stage to blastocyst) and mouse teratocarcinoma cells. In each case, the pattern of methylation was examined by use of the restriction enzymes Hha I and HPA II HPA II, which cut DNA at the sites 5'GCGC and 5'CCGG respectively, when the cytosines at these sites are not methylated. Mouse embryo DNA was found to have the same level of methylation as adult mouse tissues, and no changes in methylation were seen during differentiation of the teratocarcinoma cells. The ratio of 5-MeCyt/Cyt in DNA was measured by high performance liquid chromatography for the differentiating teratocarcinoma cells and for several adult mouse and rabbit tissues. The variation between tissues or between teratocarcinoma cells at different stages of differentiation was less than 10 percent. These results are discussed in view of proposals that 5-MeCyt plays a role in differentiation.

Animals↗
PubMed2001

The mouse putative pheromone receptor was specifically activated by stimulation with male mouse urine.

To detect the biological activity of mammalian putative pheromone receptors (V1Rs and V2Rs), the mouse V1R gene was introduced into a primary culture of vomeronasal cells using the adenovirus expression system, and the response of these cells to mouse urine was analyzed by calcium imaging. These cells specifically responded to male but not female mouse urine. This response was attenuated by pertussis toxin, a specific inhibitor of G-protein G(ialpha)/G(oalpha) coupling from receptors. Our findings indicate that a putative pheromone receptor was specifically activated by mouse urine, a major source of mouse pheromones, and suggest that G(i)/G(o) are functionally coupled with the receptor.

Amino Acid Sequence↗
PubMed1997

Expression of the long arm sequence of mouse laminin alpha1, beta1, or gamma1 chain in COS1 cells and assembly of monkey-mouse hybrid laminin.

Mouse laminin alpha1, beta1, or gamma1 sequence covering truncated regions of the long arm was transiently expressed in monkey COS1 cells. Unlike natural laminins, in which only alpha beta gamma trimers are selectively assembled and disulfide-bonded at the long arm, a large fraction of mouse chains formed disulfide-bonded homopolymers. However, a small fraction of mouse beta1 (or gamma1) formed hybrid beta1gamma1 dimers with endogenous monkey gamma1 (or beta1). These hybrid beta1gamma1 dimers formed alpha1 beta1 gamma1 trimer with monkey alpha1. Mouse alpha1 also formed disulfide bonds with monkey beta1gamma1 dimer. Thus, a common mechanism is shared by laminin chains of different animal origins. Sequences in the E8 region at the C-terminal end of the long arm were crucial for this chain-selective assembly. When the C-terminal sequence of mouse beta1 long arm was extended beyond the alpha-loop, the hybrid trimer formation was diminished. This supported the model of altered chain arrangement around the alpha-loop.

Animals↗
PubMed1986

Isolation and characterization of the cDNAs corresponding to mRNAs abundant in undifferentiated mouse embryonal teratocarcinoma stem cells, but not in differentiated mouse parietal endoderm cells.

As retinoic acid (RA) and dibutyryl cAMP (cAMP) treatment induces differentiation of mouse teratocarcinoma F9 cells into parietal endoderm cells in vitro, we initiated studies on the molecular mechanisms underlying early mammalian cell differentiation in this system. We constructed cDNA libraries on the poly(A)+RNAs extracted from the undifferentiated F9 cells, and screened for cDNA sequences expressed abundantly in F9 cells, but not in terminally differentiated mouse parietal endoderm PYS-2 cells. Six different cDNA clones were isolated and characterized. The levels of RNAs hybridizable to these clones were at most 5 to 24% in the PYS-2 cells when compared with those in the undifferentiated F9 cells. The six clones were classified into two groups on the basis of their responses to the RA and cAMP treatment. In F9 cells, the levels of RNAs hybridizable to the first group, which contained four clones, were decreased within 72 h after the addition of RA and cAMP, while those of the second group, which contained the remaining two clones, did not decrease significantly. One of the first group clones, named pF9-1, corresponded to the mouse "early transposon-like elements" and another, named pF9-4, hybridized to multi-size RNAs extracted from the undifferentiated F9 cells. The mouse genomic DNA sequences hybridizable to pF9-4 were repeated approximately 5,000 times, and comprise a new gene family, the expression of which is developmentally regulated in mouse F9 cells.

Animals↗
PubMed1985

Evidence for plasma membrane impermeability to small ions in acrosome-intact mouse spermatozoa bound to mouse zonae pellucidae, using an aminoacridine fluorescent pH probe: time course of the zona-induced acrosome reaction monitored by both chlortetracycline and pH probe fluorescence.

Previous studies have shown that capacitated mouse spermatozoa bind to zonae pellucidae of mouse eggs with acrosomes apparently intact. The question addressed in this study was the following: are the membrane permeability barriers of the apparently acrosome-intact sperm still retained or is there a preliminary stage of the acrosome reaction in which these barriers are lost and the intracellular space becomes accessible to extracellular substrates? The experimental approach was to use the fluorescent pH probe 9-amino-3-chloro-7-methoxyacridine, which accumulates in intracellular spaces of lower pH than the suspending medium with the result that the cells become fluorescent. Freshly capacitated mouse spermatozoa bound to isolated zonae showed uniform fluorescence over the head and midpiece with this fluorescent probe at early times of binding. The fluorescence was abolished by NH4+ and nigericin, agents that equilibrate H+ across cell membranes. At these early times of binding, the acrosomes were fully intact as judged by chlortetracycline fluorescence pattern, which itself was unaffected by either N4+ or nigericin. The time course of the loss of this chlortetracycline pattern characteristic of acrosome-intactness was closely paralleled by loss of fluorescence of 9-amino-3-chloro-6-methoxyacridine over the first 90 min; thereafter, loss of the chlortetracycline pattern was somewhat more rapid. This result shows that acrosome-intact sperm bound to zonae pellucidae retain the permeability barriers of the plasma membrane to small cations; no evidence was found for an early stage of membrane "leakiness" preceding the acrosome reaction. The ionophore A23187 induced a very rapid acrosome reaction in sperm bound to isolated zonae, as judged with both fluorescence probes. This rapid reaction was partially inhibited by 3-quinuclidinyl benzilate, which, in the absence of ionophore, completely blocks the occurrence of the acrosome reaction in sperm bound to zonae. This suggests involvement of a specific calcium entry mechanism in the acrosome reaction of mouse sperm induced by mouse zonae pellucidae.

Acrosome↗
PubMed1980

Interferon production by human-mouse hybrid cells: dominant mouse control of superinduction and priming.

We have examined the production of interferon by a number of human-mouse hybrid clones in response to polyriboinosinic acid:polyribocytidylic acid copolymer [poly(rI).poly(rC)] all of which produced both human and mouse interferons when stimulated with a virus. Their capacity to be superinduced and primed for interferon production in response to poly(rI).poly(rC) was compared to that of the parental human and mouse cells. It was found that the hybrids responded in a way similar to their mouse cell parents, indicating dominant mouse control of both the priming and superinduction phenomena.

Animals↗
PubMed1986

Characterization of three mouse monoclonal antibodies that react with high-molecular-mass glycopeptides isolated from F9 mouse teratocarcinoma cells.

Three IgM mouse monoclonal antibodies, NL-9, Thy-22, and HL-5, which were produced primarily against human hematopoietic cells, were tested for their reactivity with various mouse cell lines and were found to react predominantly with mouse embryonal carcinoma cells. Thy-22 reacted with 2-cell-stage mouse embryos, whereas the other two antibodies were not reactive at this stage. All three antibodies, however, reacted with 8-cell-stage embryos. At the blastocyst stage, Thy-22 reacted with the entire surface of the trophectoderm cells, whereas the reactivity of NL-9 and HL-5 was weaker and was polarized on the mural trophectoderm. Immunohistological examination of 6th-day mouse embryos using anti-complement immunofluorescence demonstrated that the embryonic ectoderm was positive for all three antibodies: the reaction of NL-9 and Thy-22 was uniformly distributed over these cells, whereas HL-5 predominantly stained the luminal aspects of the cells lining the proamniotic cavity. Visceral-endoderm cells and trophoblastic cells were positive with all three monoclonal antibodies, whereas the parietal endoderm, extraembryonic ectoderm, and ectoplacental cone were negative. In 19th-day fetuses and adult tissues, certain epithelial cells were stained by these three antibodies. The biochemical nature of the antigens detected was also investigated. Farr's assay showed that both NL-9 and Thy-22 precipitated approximately 10% of the high-molecular-mass glycopeptides isolated from F9 cells, while HL-5 reacted with about 5% of these glycopeptides. The reactivity of the three antibodies against the glycopeptides was completely inhibited by the presence of X-hapten-conjugated silica.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Evolution of gene regulation as revealed by differential regulation of the chicken lysozyme transgene and the endogenous mouse lysozyme gene in mouse macrophages.

Lysozyme gene expression is a marker for macrophage differentiation in vertebrates. We have previously shown that expression of the complete chicken lysozyme gene domain in macrophages of transgenic mice is directly correlated to the copy number of integrated transgenes. Thus, the chicken lysozyme locus in the mouse acts as an independent regulatory unit irrespective of its random position in the host genome. This finding allowed a comparative analysis of the regulation of the endogenous mouse lysozyme M gene and the chicken lysozyme transgene in the same animal. We demonstrate by transcript analysis of total tissue RNA and by in situ hybridization, that both genes are expressed in macrophages. In macrophages of the same animal the regulation of both genes in response to external signals was distinctly different: the lysozyme transgene responded to various agents influencing macrophage activation, in contrast, mouse lysozyme RNA levels remained unchanged under these conditions. Thus, as in chicken macrophages, the chicken lysozyme expression level in mouse macrophages is coupled to the macrophage activation status, while the mouse lysozyme is not. Our results suggest, that the cis-regulatory elements of lysozyme genes have evolved more rapidly than the function and expression of the trans-acting factors involved in the regulation of macrophage-specific gene activation.

Animals↗
PubMed1996

Pregnenolone-7 beta-hydroxylating activities of yeast-expressed mouse cytochrome P450-1A1 and mouse-tissue microsomes.

In many tissues from different species, pregnenolone and dehydroepiandrosterone (DHEA) are hydroxylated mainly at the 7 alpha position by a cytochrome P450 (P450)-containing microsomal enzyme complex. In addition, 7-hydroxysteroids have been shown to activate immune processes in mice. The reported production of 7 beta-hydroxypregnenolone and 7 beta-hydroxy-DHEA was not supported by formal identification, and the P450 responsible for 7 alpha-hydroxylation and 7 beta-hydroxylation of pregnenolone and DHEA have not been identified. Based on results of analyses by crystallization to constant specific activity and gas chromatography/mass spectrometry, we report that mouse-liver and mouse-brain microsomes carried out 7 beta-hydroxylation of pregnenolone and DHEA, and that yeast-expressed mouse cytochrome P450-1A1 (P450 1A1) transformed pregnenolone into 7 beta-hydroxypregnenolone (Km = 25.1 +/- 0.4 microM, turnover number = 979 +/- 30 pmol.min-1.nmol-1 mouse P450 1A1). Neither 7-hydroxy derivatives of DHEA nor 7 alpha-hydroxypregnenolone was produced by P450 1A1. The presence of P450 1A1 in liver and brain microsomes was shown by Western blot analysis, and induction of mouse P450 1A1 by beta-naphthoflavone resulted in increased 7 beta-hydroxylation of pregnenolone in liver microsomes. Studies of the brain-microsome 7 beta-hydroxylating enzyme with pregnenolone or DHEA gave Km of 5.0 microM and 4.9 microM, respectively, and Vmax of 4.5 pmol.min-1.mg-1 and 6.1 pmol.min-1.mg-1, respectively, and showed the absence of cross-inhibitions between the two steroids. These findings indicate that, in addition to unidentified P450, P450 1A1 is involved in 7 beta-hydroxylation of pregnenolone and may contribute in part to the production of the 7-hydroxylated steroids necessary for activation of immune defenses.

Animals↗
PubMed2005

Lung pathology of pale ear mouse (model of Hermansky-Pudlak syndrome 1) and beige mouse (model of Chediak-Higashi syndrome): severity of giant lamellar body degeneration of type II pneumocytes correlates with interstitial inflammation.

The authors have recently reported the presence of characteristic foamy swelling/degeneration (giant lamellar body degeneration, GLBD) of type II pneumocytes in the lungs affected by Hermansky-Pudlak syndrome (HPS)-associated interstitial pneumonia (HPSIP), and proposed the hypothesis that GLBD may be the triggering factor in the development of HPSIP (Virchows Arch 2000; 437: 304-13). The purpose of the present paper was to investigate the lung pathology of pale ear (ep) mouse, a mouse model of HPS1, and of beige (bg) mouse, a mouse model of Chediak-Higashi syndrome (CHS) with a reference to GLBD and associated pathologic changes. GLBD was found in both ep and bg mice soon after birth, and increased in severity as the mice grew older. Younger mice had only GLBD with no evidence of interstitial change. Aged bg mice showed the most prominent GLBD and patchy areas of alveolar collapse accompanied by lymphocytic infiltration and slight fibrosis. Aged ep mice with less severe GLBD than bg mice of comparable ages also had a slight tendency to develop interstitial inflammation but no fibrosis. The pneumocytes with GLBD were immunoreactive for surfactant protein B and composed of giant lamellar bodies ultrastructurally, findings which were almost identical to those of human GLBD. The results of the present study support the hypothesis that GLBD may play an important role in the development of HPSIP. Ep and bg mice, especially the latter, may be useful mouse models of HPSIP.

Animals↗